123rd Meeting Minutes

Minutes - May 3-4, 2016

The National Advisory Council on Drug Abuse convened its 123rd meeting at 2:00 p.m. on May 3rd, 2016 in Conference Rooms C & D, 6001 Executive Boulevard, Bethesda, Maryland. The closed portion of the meeting held on May 3rd was for the purpose of reviewing applications for Federal grant assistance and was open only to Council members and Federal employees. The open portion, which was open to the public on May 4th, began at 8:30 a.m. The Council adjourned on May 4, 2016 at 3:10 p.m. 

Council Members Present
Anne Andorn, M.D.
Judith Auerbach, Ph.D.
Laura Bierut, M.D.
Julie Blendy, Ph.D.
Regina Carelli, Ph.D.
John Carnevale, Ph.D.
H. Westley Clark, M.D., J.D.
Arthur Dean, M.A.
Marie Gallo Dyak
James Hildreth, M.D., Ph.D.
Lisa Marsch, Ph.D.
Edward Nunes, M.D.
Steffanie Strathdee, Ph.D. 

Council Members Absent
Jay Giedd, M.D.
Robert Rancourt, J.D.
Eric Verdin, M.D. 

Council Chair
Nora Volkow, M.D.

Executive Secretary
Susan Weiss, Ph.D.

Federal Employees Present

Members of the Public Present

Kathryn Kaplan - Ogilvy Public Relations
Melissa Mera A. - Bright Idea, LLC
Ann Rea - Kelly Services, Inc.
Juli Rose A. - Bright Idea, LLC
Jen Sizemore A. - Bright Idea, LLC
Susan Taylor
Albert Terrillon - Community Anti-Drug Coalitions of America
Roy Walker - Synergy Enterprises, Inc.
Patrick Zickler - The Palisades Group, LLC 

Closed Portion of the Meeting – May 3, 2016

1. Call to Order

   This portion of the meeting was closed to the public in accordance with sections 552b(c) (4) and 552b(c) (6), Title 5, U.S. Code and section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2).
   
   Dr. Nora Volkow, Director, NIDA, called the meeting to order and welcomed the Council and staff. She reminded those present that the Federal Advisory Committee Act applies to Council meetings and that this portion of the meeting was closed to the public.
   
   Dr. Susan Weiss, Executive Secretary, summarized relevant NIH policies, provided detailed instructions on Council review procedures, and reminded those present about NIH confidentiality and conflict of interest policies. 

2. Application Reviews

   In turn, the Director or a designee for the Division of Epidemiology, Services and Prevention Research, the Division of Therapeutics and Medical Consequences, and the Division of Neuroscience and Behavior presented their applications for consideration by the Council. For each, Council provided concurrence with the initial scientific reviews en bloc. Council also approved Administrative Supplements. Relevant applications were presented to Council for Special Council Review, and Council agreed with program assessments. All Trans-NIH Initiatives, i.e., Common Fund applications and NIDA Secondary applications also received Council concurrence. 

   Members must absent themselves from the Council meetings during discussion of, and voting on, individual applications from their own institutions or other applications in which there is a conflict of interest, real or apparent. Conflicts of interest statements were signed by each member of the Council. Members were not required to leave if an application in conflict with that member was acted upon en bloc. 

Open Portion of the Meeting – May 4, 2016

1. Call to Order

   Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order and welcomed all attendees. She began by welcoming and introducing new council members: Dr. H. Westley Clark, Ms. Marie Gallo Dyak, Dr. Lisa A. Marsch, and Dr. Edward V Nunes, Jr.

   Dr. Clark is currently the Dean’s Executive Professor of Public Health at Santa Clara University in Santa Clara California. He is formerly the Director of the Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, U.S. Department of Health and Human Service, where he led the agency’s national effort to provide effective and accessible treatment to all Americans with addictive disorders. Dr. Clark was also the former chief of the Associated Substance Abuse Programs at the U.S. Department of Veterans Affairs Medical Center in San Francisco, California and a former associate clinical professor, Department of Psychiatry, University of California at San Francisco (UCSF). Dr. Clark served as a senior program consultant to the Robert Wood Johnson, Substance Abuse Policy Program, as a co-investigator on a number of National Institute on Drug Abuse-funded research grants. He worked for Senator Edward Kennedy as a health counsel on the US Senate Committee of Labor and Human Resources.

   Marie Gallo Dyak is Executive Vice President of Program Services and Government Relations to the Entertainment Industries Council, Inc. She is responsible for concept development and implementation of EIC programs and special projects primarily involving the entertainment industry and health and social issues. She is also Co-Executive Producer of the PRISM Awards. The PRISM Awards spotlights creative contributions that best exemplify the entertainment industry's sincere efforts to use its unique platform with access to audiences to present accurate information through depiction of substance use disorders and mental health issues. Ms. Dyak is an Emmy® Award winning producer, having produced educational and training videos on such topics as substance abuse and addiction, foster care, multicultural families, PET cardiac scanning procedures, and inhalant abuse. 

   Dr. Lisa A. Marsch is Director of the Center for Technology and Behavioral Health (www.c4tbh.org), the Director of the Dartmouth Psychiatric Research Center, and a faculty member within the Department of Psychiatry at the Geisel School of Medicine at Dartmouth College. Dr. Marsch has led a line of research focused on the development and evaluation of technology-based interventions targeting substance abuse treatment, as well as HIV prevention, mental health, and other areas of behavioral health. These technology-based therapeutic tools reflect an integration of science-based behavioral interventions with evidence-based informational technologies. This research has provided novel empirical information regarding the role that technology may play in improving the prevention and treatment of substance use disorders and other behavioral health issues by improving quality of care, access to care, and treatment outcomes, while reducing costs of care. 

   Dr. Edward Nunes Jr. is Professor of Psychiatry at Columbia University and New York State Psychiatric Institute and a Board Certified psychiatrist and addiction psychiatrist, who has devoted his career to the development and evaluation of new treatments for substance use and related mental health conditions. Dr. Nunes has been principal investigator or collaborator on numerous NIH-funded studies and, since 2000, has served as principal investigator of the Greater New York Node in NIDA’s Clinical Trials Network, which is committed to the evaluation and dissemination of effective treatment methods for substance use disorders in community-based settings. He thus has extensive experience in the implementation and evaluation of treatment innovations in “real-world” treatment settings. His past work includes the development and evaluation of medications and behavioral treatments for co-occurring alcohol/drug and mood/anxiety disorders, treatments for cocaine and opioid dependence, design of treatment evaluation studies, and methods for training community-based clinicians in evidence-based practices. 

   Dr. Volkow reminded the Council and audience that the meeting was open to the public in compliance with the Government in the Sunshine Act and indicated that time would be provided for public comment. She then called attention to future Council meetings: September 8, 2016, and February 15, 2017. Beginning in September, NIDA Advisory Council meetings will be a one-day meeting. CRAN Joint Council meetings will be held in May of each year starting in 2017.

2. Consideration of the Minutes of Council

   The Minutes of the NIDA January 2016, as well as the January 2016 CRAN Joint meeting were unanimously approved as written. 

3. NIDA Director’s Report - Nora Volkow, M.D., Director, NIDA

   Dr. Volkow began her presentation with staff changes at NIDA. Dr. Joni Rutter, former Director of the Division of Neuroscience and Behavior (DNB), took a position with the Precision Medicine Initiative at the Office of the Director, NIH. Dr. Roger Little is now the Acting Director for DNB, and the process for seeking a permanent Director has been initiated. 

   Dr. Volkow then gave an update on the budget. The Presidential Budget for FY 2016, is a 4 percent increase over FY 2015’s budget and places NIDA’s total budget at a little over $1 billion, with the AIDS allocation at approximately one third of the total budget; however, due to reconfiguration of NIH’s Office of AIDS research priorities, there is a slight decrease in overall AIDS funding. The total increase for NIDA from 2015 to 2016 is approximately $ 35 million. The FY 2017 proposed budget is the same as that for 2016. 

   She then provided NIDA’s program level in appropriated and constant 1998 dollars. Even though the total appropriate dollar amount has been steadily increasing, NIDA’s purchasing capacity is the stable at 1998 dollars. The consequences of such a limited purchasing power, is NIDAs limited ability to fund and support the increasing number of scientific research applications. 

   Turning to what is new at NIH; Dr. Volkow began with the Precision Medicine Initiative (PMI), which comprises two components. The large cohort component, and the cancer precision medicine initiative. $250 million were allocated in FY 2016 for the PMI, of which $130 million of the total allocation is being used to build the large cohort. The PMI has already issued multiple funding opportunities: PMI Cohort Program Coordinating Center (U2C); PMI Cohort Program Healthcare Provider Organization Enrollment Centers(UG3/UH3); PMI Cohort Program Participant Technologies Center (U24); PMI Cohort Program Biobank (U24); PMI Cohort Program Direct Volunteers Pilot Studies (OTA); and Communications Support for the PMI Research Program at NIH (OTA). In addition, Eric Dishman, formerly Vice President and Intel Fellow of Intel Corporation’s Health and Life Science Group, was named Director, PMI Cohort Program. 

   Dr. Volkow then spoke about the continued rise in awareness of drug abuse and addiction as a major public health concern, including among members of both major political parties in the US. She spoke of her invitations to and involvement at hearings in both the House and the Senate on March 16 and April 7, 2016, respectively, on the President’s 2017 NIH Budget Request. She stated that the prescription opioid abuse epidemic was of great concern to both Democratic and Republican members and that their increased awareness provides an opportunity for NIDA to enhance recognition of addiction as a medical disease, and to advance the science behind it. 

   Dr. Volkow went on to highlight NIDA priorities, beginning with Prevention Research. She began with an update on the Adolescent Brain Cognitive Development (ABCD) project, which is the largest prospective study investigating brain development. The goal is to recruit and follow 10,000 children over a 10 year period with detailed phenotypic characterization and frequent evaluations, including brain imaging, during the critical transition period from 9-10 years old to ~age 20. The ABCD study will provide open access to data that will yield critical insights into the foundational aspects of adolescence that shape a person’s future, including brain structure, function, and functional connectivity. Other indicators of development, such as educational achievement and physical growth will also be measured. The study will use a school-based recruitment strategy; it has received IRB approval; the informatics systems have been developed for data collection; a “Train the Trainers” meeting was held on April 18-20, 2016; pilot testing and protocol refinement are ongoing; and full recruitment is expected to begin in the fall. Drs. Susan Weiss and Gaya Dowling have been instrumental in initiating these efforts, and reaching out to other partners, such as the Centers for Disease Control and Prevention (CDC), which already works with schools across the U.S. as part of their data collection efforts. An ABCD website has been developed (www.ABCDstudy.org) to help with outreach efforts, as well as serve as a resource for information and education materials for teachers, parents, and teenagers. 

   NIDA, in partnership with other NIH Institutes (NIAAA, NIMH, NINDS, and NCCIH) hosted a well-attended scientific meeting titled “Marijuana and Cannabinoids: A Neuroscience Research Summit” on March 22-23, 2016. NIDA previously sponsored a meeting on marijuana in 1999 that led to a follow up forum in 2000 by the Institute of Medicine (IOM) to address the state of the science regarding the potential medical applications for marijuana. And at that time, the IOM concluded that the evidence of marijuana’s therapeutic benefits was very limited, except to improve symptoms of nausea and wasting in individuals with cachexia. The recent meeting was very successful, in part because of the active involvement of NIDA’s Office of Science Policy and Communications, as well as participation by Dr. Weiss and other NIDA Divisions. 

   By way of summary, there has been an enormous amount of information and knowledge gained over the past 16 years on the endogenous cannabinoid system. This in turn, has helped us better understand the processes underlying marijuana’s rewarding and addictive properties, and its other adverse consequences; as well as the potential for therapeutic development of the cannabinoid system. A constituent of the marijuana plant, cannabidiol, has shown positive effects in reducing severe seizures in children with epilepsy, and a formulation developed by GW Pharmaceuticals (Epidiolex) is in phase 3 clinical trials now. GW is working with FDA to fast track their product for approval, pending final clinical trial results. Delta 9-tetrahydrocannabinol is also being studied for its possible analgesic and antispasticity effects. However, repeated administration of a cannabinoid agonist down-regulates the cannabinoid receptor and leads to tolerance. Thus, it is particularly important to understand the physiology of the endogenous cannabinoid system in order to best exploit its therapeutic potential. 

   Dr. Volkow then went on to praise Dr. Courtney Miller, a NIDA funded junior investigator at The Scripps Research Institute, for receiving the Presidential Early Career Award for Scientists and Engineers (PECASE). On February 18, 2016, President Obama named 105 researchers as PECASE recipients, the highest honor bestowed by the U.S. Government on science and engineering professionals in the early stages of their independent research careers. Dr. Miller was recognized for her study on the prevention of substance abuse relapse triggered by drug-associated memory. 

   Dr. Volkow presented new NIDA Funding Opportunity Announcements (FOAs): 1) Role of Astrocytes and Astrocytic Networks in Drug Abuse (R01) and (R21), which encourages research examining the effects of drugs of abuse on the structural connectivity of astrocytic networks within the CNS, and the generation, processing, and spatiotemporal control of activities within these networks; and 2) Application of Big Data Analytics to Drug Abuse Research (R01), to support the use of Big Data analytics to reveal deeper or novel insights into the biological and behavioral processes associated with SUDs. Both FOAs were issued in March, 2016. 

   Dr. Volkow then discussed NIDA’s Treatment Research priority area, focusing on the continuing opioid epidemic. She presented statistics from the CDC showing that from 1999-2014 there has been a steady and alarming increase in opioid analgesic overdose deaths in the U.S., propelled by the abuse of prescription opioids. Recognition of the urgency of addressing this epidemic prompted an annual Prescription Opioid Summit, hosted for the past 5 years by U.S. Representative from Kentucky, Harold Rogers. This year’s National Prescription Drug Abuse and Heroin Summit was held in Atlanta, GA on March 29, 2016. It is a highly visible and well-attended meeting, with over a 1000 attendees, including the President. 

   At that meeting, Dr. Tom Frieden, Director of the CDC, presented a graphic of drug poisoning death rates that have increased in almost every state from 2010 to 2014, with West Virginia leading, followed by New Mexico, and New Hampshire. CDC data indicate that this rise is due to a 4.5 fold increase in deaths from heroin overdose, despite multiple efforts and strong campaigns to contain the epidemic. 

   Dr. Volkow also described the alarming rise in heroin use in the past month and year; however, the increasing overdose deaths far exceed the increasing use, suggesting that other factors may be responsible, especially the sudden appearance of the very potent opioid fentanyl in drug seizures reported by the National Forensic Laboratory Information System in 2013 and 2014. Individuals that use heroin may be using fentanyl in combination with heroin (with or without their knowledge). 

   She then moved on to President Barack Obama’s presentation at the summit. He was on a panel that included a clinician and former substance user. He stated “… we need to recognize that addiction is a disease. If we treat addiction like a crime, then we’re doing something that’s….ineffective.” And “…taking parity seriously so that mental health issues and addiction issues are treated as a disease in the same way that if somebody came in with a serious medical illness that it’s treated.” His statements support the mission of NIDA, and reflect the changing perspective and recognition of addiction as a disease. 

   However, the infrastructure is not sufficient to care for individuals with addiction and provide them medication-assisted treatments (MAT), which have been shown to be effective for opioid use disorders. Therefore, NIDA is supporting implementation research on MAT to help solve the infrastructure problem and improve outcomes. One of these efforts is a trial of long acting Naltrexone (Vivitrol) in criminal justice populations. Vivitrol, an extended-release opioid antagonist, was provided to volunteer parolees with opioid addiction as a monthly injection for 6 months. This group was compared to those who chose community treatment, including methadone or Suboxone (buprenorphine). The results showed that the relapse frequency for those that were treated with Naltrexone is significantly lower at week 25 than those in community treatment. In addition, there were 7 overdose deaths in the community treatment vs. zero (none) in the Naltrexone group over a period of 78 weeks. 

   Another effort by NIDA to improve treatment for opiate addiction is the use of extended release implanted buprenorphine (Probuphine). Probuphine is designed to release sustained therapeutic drug levels in patients with opioid addiction for up to six months. This MAT would be especially beneficial in rural communities that do not have access to methadone clinics or may not have physicians that can prescribe buprenorphine regularly and on demand. FDA approval was pending but expected soon. 

   The last effort that Dr. Volkow presented is a NIDA funded study conducted by Dr. Kim Janda at the Scripps Institute in California. Dr. Janda developed a conjugate vaccine that ablates lethal doses of fentanyl class drugs. Testing in humans is still pending; however the success and potential to prevent an emerging problem with the use and abuse of fentanyl is very exciting. 

   Dr. Volkow then went on to NIDA’s last research priority area: HIV and drugs. A substantial consequence of injection drug use is hepatitis C infection, which has increased between 2006 and 2012. HCV related deaths rose from 11,000 in 2003 to 19,358 in 2013 and this is likely to be an underestimation. HCV is a disease that progresses slowly; however, when symptoms begin to appear, on average 10-20 years after exposure, they are often advanced stages of hepatic fibrosis that lead to hepatic cancer and cirrhosis. 

   At this time, there aren’t enough population data available on outcomes HCV treatment for injection drug users. However, a 2013 Clinical Infectious Diseases published study by NK Martin, used a modeling approach to determine the number of people needed to treat with both antiviral therapy and MAT in order to produce an 80 percent reduction in HCV prevalence within 10 years. The study showed that implementing antivirals and aggressive opioid substitution therapy (MAT), with a syringe exchange program for 40% of the population infected with HCV, would achieve that exact goal. Another recent study by Akyar et al., Emerging Infectious Diseases, May 2016; 22(5): 907-909, showed that less than 1 percent of suburban New Jersey heroin users that were diagnosed with HCV received treatment. 

   The CDC recently released data on the vulnerability to HIV/HCV co-infections among IDU. They found 220 counties ranked at the top, and that 26 states had at least one vulnerable county. The majority of the high ranked counties were in the Appalachian region. Dr. Volkow spoke about her recent visits to the states of Kentucky and West Virginia, and her most striking discovery was the lack of healthcare infrastructure. NIDA has decided to make this a priority, and has created a partnership with the Appalachian Regional Commission to fund research in this area. Applications for RFA-DA-16-015, Injecting Drug Users and consequences in Opioid Dependence, HIV and HCV, were due by April 28, 2016. This is a one-year research planning grant to improve understanding the problem’s scope, and to identify both resources and obstacles, in order to build a foundation for better intervention programs and larger-scale efforts. 

   She then provided Council members with an update on the impact of the new NIH HIV priorities on NIDA’s re-competition for HIV/AIDS funding. The Office of AIDS Research (OAR) reviewed FY 14 extramural grants eligible for renewal in FY16 (1207 grants), and 242 of them were judged to be low priority (totaling $65.2 million). These funds were taken out of NIH IC’s, with $14.2 million coming from NIDA and placed in an NIH common HIV fund. As for the intramural side, OAR reviewed FY14 projects eligible for renewal in FY16 (56 projects), and of those, 26 projects were considered low priority ($6.6 million) -- $3.3 million will be taken out of NIDA’s budget. 

   NIDA, with help from Council members, has established the following new Funding Opportunity Announcements (FOAs) to help align NIDA and OAR’s HIV priorities. PAR-16-117: Increased Knowledge and Innovative Strategies to Reduce HIV Incidence (iKnow Projects), with application due dates May 16, 2016; May 9, 2017; and May 8, 2018. The purpose is to devise optimal strategies to improve the identification of persons unaware of their HIV-1 infection and successfully link them to HIV testing, treatment, and prevention interventions. Also, to develop and examine the feasibility and acceptability of novel integrated interventions of biomedical and behavioral strategies to reduce HIV transmission in these populations. 

   The other FOAs, are in collaboration with the National Institute on Mental Health (NIMH) and the National Institute of Neurological Disorders and Stroke (NINDS). RFA-MH-17-100 (R21) and RFA-MD-17-101 (R01) Novel Strategies for Targeting HIV-CNS Reservoirs without Reactivation. Applications are due on September 9, 2016. The purpose of these FOAs is to identify HIV-1 infected cells in the CNS that are latent; develop strategies for targeting these cells in order to achieve viral silencing leading to inhibition of viral production, without pro-viral reactivation. 

   Finally, Dr. Volkow spoke about her participation at the United Nations General Assembly Special Session (UNGASS) on the World Drug Problem in April, 2016 in New York City. A report that came out of this multi-nation meeting, which is now posted on the United Nations website, states that addiction is a disease of the brain, that it should be treated rather than criminalized, that infrastructure should become available to provide such treatments, including for those currently in the criminal justice system. It also stated, consistent with President Obama’s message at the Summit, that for individuals with substance use disorders, criminalization can actually exacerbate the negative outcomes and make persons more vulnerable to continued drug use, relapse, and overdose. 

   Council thanked Dr. Volkow for her presentation and for NIDA’s efforts to work with the Appalachian Regional Commission to address the opioid/Hep C crisis head-on, as well as the work that NIDA has supported that has led to a recognition of addiction as a disease of the brain by the President, the media, and the American public. Another Council member questioned why so many Americans are using pain medications, and whether it’s a result of physical or psychic pain (or both). Council reiterated the importance of building health infrastructures and making services available to care for patients with substance use disorders, as well as those with HIV and HCV. Although NIDA doesn’t directly support infrastructure for providing services, there is strong need to fund implementation sciences research to make a bigger impact. 

4. Evidence-Based Funding: Thoughts about Extramural Research - Michael S. Lauer, M.D., Deputy Director for Extramural Research, NIH 

   Dr. Lauer began his presentation with a consideration of metrics commonly used as markers of success in the biomedical research enterprise. He spoke about an article in the Proceedings of the National Academy of Sciences (2015; 112: 9496-7), by Shapiro and Varna, from Pennsylvania State College of Medicine, that noted getting grants is a major goal of biomedical research institutions and success is measured in the total amount of grant funding acquired. They argued that such measures of success are somewhat akin to an airline boasting about how many miles its planes flew or how much fuel its planes consumed. Instead, they offered that completing funded studies, publishing results, and being cited in the literature by other researchers would be optimal goals. Dr. Lauer then related a recent travel experience during which he read the Mission and Purpose statement of Southwest airlines, which is “to deliver people where they want to go, safely, on time, with their bags, and with a smile…” all of which are quantifiable and measurable. Both of these cases led him to question what kind of metrics are most important in the medical research enterprise. 

   The Director of the National Institute of General Medical Sciences (NIGMS), Dr. Jon Lorsch, wrote an article in Molecular Biology of the Cell 2015; 26: 1578-82 entitled “Maximizing the return on taxpayers’ investments in fundamental biomedical research.” In it, he too, discusses changing our funding metrics and raises the question of whether NIH’s key metric should be the number of grants awarded or the number of investigators supported because, after all, it is investigators who do the research, not the research dollars. Dr. Lauer added, the question should be not just how many investigators are supported but how many unique individuals does the NIH support as principle investigators of research program grants. He presented a graphic that showed the number of NIH grant awardees each year from 2003 through 2015 has been approximately stable starting at 25,000 to what it is currently at 27,500. However, over the same period of time the number of people applying for NIH grants rose from about 60,000 applicants in 2003 to about 90,000 in 2015. Thus, the funding environment has become hyper-competitive and, perhaps, many of the problems seen in the world of biomedical research are symptoms of this state of hyper-competition. 

   Dr. Lauer went on to suggest that an optimal measure of success might be how many publications and citations result from NIH funded projects and investigators. He noted, however, that frequency of publication is typically dependent on the field of research and that comparing number of publications and number of citations alone would not accurately reflect the impact of research in different fields. He added that it is important to have field normalized citation metrics, and he showed two publications that support that concept. One by Diana Hicks and Paul Wouters, Nature 2015; 520: 429-31 entitled “the Lieden Manifesto for research metrics.” And the other by Bornmann and Marx called “How good is research really? Measuring the citation impact of publications with percentiles increases correct assessments and fair comparisons.” EMBO Reports 2013; 14: 226-30. 

   Dr. Lauer then presented a preliminary analysis of NIH Type 1 R01 funded applications between the years 2000-2010. Approximately 38,000 grants were funded, and these grants produced about 300,000 papers that represented the work of about 27,000 unique investigators in a little over 1000 unique organizations. Each of the papers that were cited was binned by topic and year of publication; then each paper was assigned a percentile based on the amount of times it was cited and compared with other papers for the same topic and publication year. The sum of these measurements produced the grant citation impact. All grants were divided into human and non-human studies, and when plotted followed a logarithmic function. This has been referred to in some areas of science as following a power law. An article in the Journal of Economic Perspectives 2016; 30: 185-206, written by Xavier Gabaix, an NYU professor states that “one implication of the power law is that there are many more extreme events than would occur if the distribution were Gaussian; for example, if the distribution were the result of a series of events of fixed probability, like flipping coins or rolling dice.” 

   He then went on to say that there might be yet another goal to research funding, and it goes beyond the point of citations. It would be extreme events, such as the discovery of DNA, the theory of evolution, CRISPR/Cas9, and the Women’s Health Initiative trials as examples. It would need to be objective and quantifiable. A recent publication from Sanders et al. in Cell 2015; 163: 21-23 mapped out a discovery from publicly available databases, the FDA books, the U.S. Patent Office, PubMed, the Web of Science, and others. The example he showed was for the drug Ivacaftor, for the treatment of cystic fibrosis, and the results of the study showed that 2587 scientists and 2516 institutions had worked over a period of 60 years and produced thousands of documents with some being more influential than others. These data are very helpful for understanding patterns to discovery and could help NIH make wiser investment decisions in the future. NIH has already begun to draw maps to help derive different kinds of transformative discoveries. 

   Dr. Lauer concluded his presentation by addressing the NIH Strategic Plan, specifically that the NIH, as a funding agency, has the responsibility to enhance stewardship and to excel as a federal science agency that manages by results. The goal for NIH is to not only produce evidence-based medicine, but to also practice evidence-based funding. He then thanked NIDA’s Dr. Elena Koustova for sharing with OER her data-driven SBIR project decision making. 

   NIDA Council members thanked Dr. Lauer for his presentation. Some members of Council commended OER on its databases such as RePORTER and ExPORTER for the array of information that can be used by scientists. One question that was brought up was what would qualify a particular paper or product as being transformative. The answer is that there are multiple ways of measuring and assessing the impact of a particular person or laboratory on a topic and he provided non-science related examples to describe one of the methods.

5. NIDA Intramural Program Review: Role of the Board of Scientific Counselors - Regina M. Carelli, Ph.D., NACDA Council Member and Intramural Program BSC Council Liaison, Distinguished Professor, Department of Psychology, University of North Carolina, Chapel Hill 

   Dr. Carelli started her presentation by stating that she was asked by Dr. Nora Volkow to present on her role as the NACDA liaison to the Intramural Research Program (IRP) Board of Scientific Counselors (BSC), and what she learned from this task is that the intramural review process is very rigorous and that this is not always recognized by the extramural community. She began with the IRP’s organization chart as an overview of the different branches that are overseen by Dr. Antonello Bonci. 

   The goal of the BSC review process is to assist the Scientific Director by providing a rigorous external scientific review of the IRP. The BSC consists of outside experts with scientific qualifications to serve as authorities in the fields under review. There are 12 standing regular members, and 5 ad hoc members that serve on as needed basis. The NIDA BSC meets 1-2 times per year, and every IRP scientist is reviewed at least once every 4 years. 

   The first part of the process is understanding the vision of the IRP, which is to create a world class neuroscience institute on substance use disorders (SUD); to develop and maintain an environment where cutting edge science, human studies, and drug related initiatives (that are not easily or quickly fundable outside of NIH) can thrive; and to have a highly interactive intramural-extramural environment. 

   Prior to each of the BSC meetings, the BSC members are provided a packet for each scientist being reviewed. Each packet contains a progress report on current research, including descriptions of each project and its future plans; the scientist’s current Curriculum Vitae (CV); copies of up to three recent publications; a summary of the amount of support staff, space and budget each has; a listing of former fellows and their current positions; and a copy of each scientist’s last BSC report. This information helps the BSC members better understand progress made by each scientist. 

   During the BSC meetings, Dr. Bonci, the Scientific Director, presents an overview of the state of the IRP and provides the members with updates. BSC members meet with laboratory staff, including post-baccalaureates and postdocs. These meetings are in the absence of the director, and the Principle Investigator of the lab; thus allowing the students an opportunity to present their concerns and goals in confidence. After that, each Principle Investigator being reviewed presents their research and future plans. Finally, the BSC speaks with each scientist individually to gain a full perspective and assessment of her/his alignment with NIDA’s mission. 

   Once the BSC meetings are completed, each member writes a report to address the specific criteria and rate each of the assigned scientists. Ratings are based on a 1-9 scale, with 1 being exceptional; and they cover the following six questions: 1) is the PI a recognized international leader in the field? 2) Has s/he sustained productivity and publications in top tier journals since the last BSC review? 3) Although the IRP BSC review is meant to be largely retrospective and future plans are not extensively described, what is the viability of and level of your enthusiasm for the future plans discussed? 4) Are the research accomplishments commensurate with a full professor in your academic institution or a senior scientist in industry with commensurate resources? 5) What is the PI’s level of community service to NIH and the scientific community at large? 6) What is the PI’s level of commitment as a mentor, especially taking into account staff interviews? 

   At the completion of the review, the BSC members provide a written summary to the BSC Chair. The BSC Chair then compiles all reviews, and writes a summary of the BSC discussions. The final report includes an evaluation of topics such as: quality and impact of research program; validity of approaches used to address scientific questions; level of resources (space, budget, and personnel) supplied to each investigator; and recommendations for changes in direction, resources, etc. All BSC members must approve the final written report, and it is then sent to the SD and Institute Director. 

   Dr. Carelli then moved on to how the review and report information are used. The scoring system can dictate what happens to a research direction or a PI in the lab. Any scores below 2 (outstanding) can often lead to budget cuts, and in more extreme cases, closing of an entire laboratory. In addition, the review information is used to determine if the SD’s vision is being realized with respect to the larger emphasis on impact of the science; high risk/big impact on the field of research, and relevance to the NIDA mission. 

   She then moved on to the outcomes and IRP highlights. The IRP has 3% of its publications in journals in the top 1% citation percentile ranking, and 22% in the top 10% citation percentile ranking; the IRP has hired 5 tenure track scientists, plus 3 senior world class faculty (Schoenbaum, Koob and Bradberry), and closed 9 laboratories; and per Dr. Bonci’s vision to promote a more interactive intramural-extramural partnership, the IRP has established 10 pilot projects in 2011-2015, and created the SD Fellowship for Diversity in Research (this is the first of its kind at the NIH). Other outcomes include the optogenetic-transgenic core, products to understand minimally invasive drug and gene delivery using focused ultrasound for BBB opening, and the novel rat model to study HIV associated-neurocognitive disorder (HAND). 

   They have also had patents and licenses: Dr. Amy Newman’s modafinil derivatives patent was licensed by a start-up (as a potential stimulant tx), and a second license will follow for an ADHD therapy. Also, Dr. Kenzi Preston’s mHealth patent has interested licensees. And finally, the designer drug unit findings have impacted public health policy to reduce risk posed by designer drugs. 

   Dr. Carelli concluded her presentation by sharing her perspective and lessons learned from participating in this process. The IRP sets high standards and conducts a rigorous scientific review process; scientists are working on world class, cutting-edge research; are promoting an innovative Intramural-Extramural Partnership and developing products that are one of a kind at the NIH; and all of these efforts are due to the exceptional leadership of the Scientific Director, Dr. Antonello Bonci. 

   Dr. Volkow and Council members thanked Dr. Carelli for her presentation. Council commended Dr. Bonci on encouraging his staff to engage in community service projects, such as serving on review panels, running scientific meetings, and engaging high school students in the IRP’s special summer program in Baltimore. A comment was raised on how resources, such as transgenic rats are shared with the extramural community. Dr. Bonci stated that the IRP has a repository that can be easily accessed for information and resources.

6. Office of Science Policy and Communications - Jack B. Stein, MSW, Ph.D., Director, OSPC, NIDA

   Dr. Stein began his presentation with an overview of the Office of Science Policy and Communications’ (OSPC) goals, staff and function. The goal is to ensure NIDA is the trusted source of scientific information on drug abuse and addiction. There are three branches overseen by the OSPC’s Office of the Director (OD): the Public Information and Liaison Branch led by Ms. Carol Krause; the Digital Communication Branch led by Mr. Mark Fleming; and the Science Policy Branch lead by Dr. Maureen Boyle. Dr. Stein further showed a graphic that lists all staff within the OD and branches of OSPC. He then moved on to the OSPC function for NIDA: congressional affairs, NIH and interagency activities, portfolio analysis, research dissemination, youth outreach, web management, social media, meetings and conferences, media outreach, public inquiries, and other duties as assigned. 

   He then expanded on each of these activities. OSPC is called upon by various congressional offices for information to help shape decisions and policies based on scientific evidence. This year alone, Dr. Volkow has testified to Congress on the Biology and Potential Therapeutic Effects of Cannabidiol, as well as What Science Tells Us about Opioid Abuse and Addiction. OSPC responds to congressional inquiries and Questions for the Record (QFR), provides scientific consultation on proposed legislation, and develops congressional reports. Dr. Maureen Boyle, Chief of the Science Policy Branch, and her staff coordinate responses to NIH and departmental requests; collaborate with trans-NIH and interagency workgroups on high priority policy issues, such as, opioids, marijuana, tobacco and precision medicine. All of this is done while ensuring scientific accuracy of materials being disseminated by other institutes and agencies, such as the Surgeon General’s report that will be published in September, on which NIDA staff are consulting.

   Another function of OSPC is research analysis and its link to the Strategic Plan. Staff review and summarize NIDA’s research focus, help identify gaps and needs in research, and develop and update the Research Condition Disease Classification (RCDC) system’s coding categories. More recently the RCDC added codes for Cannabinoid Research, which shows a total of 281 projects being funded at approximately $111.3 million in FY 15, including the Therapeutic Cannabinoid Research and Cannabidiol Research subcategories. 

   He then moved on to research dissemination. NIDA has developed 160 publications, with the majority published online. Two of the most popular ones are Science of Addiction, which covers the neurobiology of addiction and has had 996,539 views. The other publication is on Prescription Drug Abuse Research, the Research Report with over 1.6 million views. OSPC targets a variety of audiences including children and teens, parents and educators, patients and families, medical health professionals, as well as researchers. All publications comply with the Language Access Plan that NIH and HHS put into place to ensure publications are available in Spanish, and are also written at a low-literacy level to guarantee public access to important information. 

   Youth outreach is part of the NIDA mission, and OSPC has created several vehicles to work with youth, parents and educators. One of them is having a separate sub-website called NIDA for Teens; OSPC has partnered with Scholastic publication to embed a number of different NIDA produced materials on the risks and prevention of substance-use disorders; the National Drug and Alcohol Facts Week, that includes Chat day where teens ask program staff questions in real-time about alcohol, drugs, and any substance abuse and addiction topics; and NIDA also supports and gives the Addiction Science Award to young researchers at the International Science and Engineering Fair. 

   The NIDA website is the hub of all communications, which is why it now has its own branch Chief, Mark Fleming. The website contains approximately 8000 pages of information, it receives 2.5 million visits per month, can be easily accessed via mobile devices- it was the first fully NIH mobile design, it is disabilities compliant, and embedded are several other websites, such as the NIDA for Teens and the Easy-to-Read Drug Facts. Dr. Stein encouraged the audience to visit the NIDA website and search through its expansive pages of information, especially the Director’s Page, which contains interesting cutting edge topics. Furthermore, NIDA social media outlets are managed by Sarah Smith, and include Twitter, Facebook, YouTube, NIDATV, Linked In and Periscope. All of these have a growing number of followers and users, and ensure that NIDA related information is widely disseminated. 

   OSPC also coordinates many science meetings. Dr. Stein listed a few that have been conducted this past year, including Society for Neuroscience/Mini Symposium on Addiction (NIDA/NIAAA); American Psychiatric Association (APA) Annual Conference/Addiction Track; American Society for Addiction Medicine (ASAM); College on Problems of Drug Dependence (CPDD); Community Anti-Drug Coalitions of America (CADCA); and Marijuana and Cannabinoids: A Neuroscience Research Summit. This last conference was conducted in collaboration with four other NIH institutes. He then spoke about the media outreach efforts, where OSPC receives and responds to approximately 70 press calls per month, issues press releases on a regular basis, and works closely with the University of Michigan on the Monitoring the Future survey to capture and present results. 

   Another important function of the office is health care provider outreach efforts. NIDAMED on the home website offers multiple resources to health care providers, including medical school curriculum, screening tools (NIDAMED ASSIST), opioid prescribing online CME/CE modules, and currently under development, an adolescent CME/CE tool. This latter tool is in development with the collaboration of multiple medical associations, such as the American Society of Addiction Medicine, and the American Academy of Pediatrics to name a few. 

   Finally, OSPC staff receive over 500 inquiries per month from the public, and the majority from substance users and their families. OSPC responds to the majority of the requests, and serves as a resource by referring many inquirers to other agencies, such as SAMHSA or ASAM, and professionals in their area that can provide assistance. 

   Dr. Volkow and Council members thanked Dr. Stein for his presentation. Council members wanted to know the relationship between OSPC and the White House’ Office of National Drug Control Policy. Dr. Stein ensured them that it was a very strong and inclusive relationship. Some current staff at OSPC had previously been at ONDCP and thus have a good understanding on best approaches and practices. Another question was on how OSPC responds to callers that don’t know where to turn for help with an SUD. Dr. Stein informed them that the NIDA Website has on its home page a section called “Looking for Treatment?” that connects them to the SAMHSA Treatment locator and offers a help call number; in addition there is a Commonly Abused Drugs Chart that has information on frequently asked questions. 

7. Overview of the Population Assessment of Tobacco And Health (PATH) Study and Highlighted Findings From Wave 1 - Kevin Conway, Ph.D., Deputy Director, DESPR, NIDA

   Dr. Conway began his presentation with an overview of the PATH Study design. The PATH Study is a nationally representative longitudinal study of tobacco use, its determinants, and its impact; it is funded by the FDA Center for Tobacco Products, and is administered by NIDA; it was also developed by FDA and NIH with assistance from Westat and their scientific partners. The study awarded its first contract in 2011 and started Wave 1 in 2013, currently the project is in Wave 3, with expectations to begin Wave 4 in late 2016. 

   He then went on to describe Wave 1 design features. Wave 1 is a longitudinal cohort design of a nationally representative sample of 45,971 U.S. civilian, non-institutionalized population ages 12 and older (32,320 are adults 18 years and older, and 13,651 are youth between the ages of 12-17 years). The sample includes never, current, as well as, former tobacco users. A four-stage stratified probability sampling design was used, representing156 clusters of counties in the U.S., and further broken out into 6000 segments, information was sent to 169,000 mailing addresses, and samples were obtained from those households. Up to two adults were sampled from each household. They were oversampled for tobacco use to supplement the sample for tobacco users. In addition, the study oversampled for African Americans, and young adults between the ages of 18-24 years, with up to two youths sampled per household. The weighted response rate for the household screener was 54 percent, and the weighted response for the adult interview was 78 percent for the youth in treatment. A variety of different tobacco products were assessed in the detailed questions in Wave 1. 

   Dr. Conway then went on to describe the Wave 1 questionnaire instruments and methodology, such as the Audio Computer-Assisted Self-Interviewing (ACASI) method for the parent interview. In addition, PATH partnered with the CDC to collect extensive bio specimen samples. He then went on to describe the different types of bio specimen (urine, blood, and buccal) samples that have and will be collected for each Wave of the study. For Wave 1, which has been completed, only adults 18 years and older provided urine and blood specimens. The plan for Wave 4 is to perform a refreshment sample for the entire study; this is to recapture approximately the full sample size in Wave 1 and ensure that it is a national representative. Many of the youth from Wave 1 would be reintroduced in Wave 4 and Wave 6 as adults, and all bio specimens at that time would be collected. This is being done to capture exposure to tobacco products for both validation and quantification purposes. 

   Wave 1 study data on flavored tobacco products use among U.S. youth was published by Ambrose et al., in JAMA 2015. The data show that approximately 80 percent of youth sampled, ages 12-17 years, were using flavored tobacco products, which include e-cigarettes, hookah, and smokeless products. Key findings presented at the presidential plenary indicate approximately 20 percent of youth reported ever using tobacco products. The youth age 15-17 have a much higher use estimate than the younger 12-14 year group. And among those, males have a higher estimate for tobacco product use, with one exception, and that is the use of hookah among females is significantly more common. Although the PATH study is not a surveillance study, there is great interest as to how the data compare with 2014 National Survey on Drug Use and Health (NSDUH) by age. Estimates from PATH are within 1 percent of the confidence interval with national surveillance systems. 

   Moving on to adult reporting, 28 percent used tobacco someday for cigarettes, with 20 percent everyday use. Prevalence estimates for adults by age group indicate that it is highest among 18-24 year olds, and nearly as many of this age group used hookah as they did cigarettes. Males in the adult group also reported a great difference in use. Comparisons of PATH results to two different national surveys, the 2014 National Survey on Drug Use and Health (NSDUH) and the 2014 National Health Interview Survey (NHIS) indicate rates are very similar and fall within the confidence interval. To note, each of those surveys define “current use” differently, and the PATH data is compared according to each of the surveys. NSDUH and PATH Study comparison define current use for cigarettes, any cigar, and smokeless tobacco as use within the past 30 days. NHIS and PATH Study define current use for cigarettes as smoking at least 100 cigarettes in lifetime and currently smoking every day or some days; NHIS and PATH Study comparison define current use for e-cigarettes as currently using every day or some days with no lifetime threshold. 

   Dr. Conway then moved into results from papers that are in progress, and stated that the focus of NIDA is on associations in Wave 1 between tobacco use, drug or alcohol use, and mental health. One of the papers on Co-occurrence of Tobacco Product Use, Substance Use, and Symptoms of Mental Health Problems in youth using MEPS data show decreases in cigarette consumption across the population, but it does not decrease among individuals with mental illness; furthermore, the difference in smoking rates between those with and without mental illness are only increasing over time. Wave 1 PATH study data in progress for youth looked at the following: independent variables are self-reported ever and current use of tobacco products; and dependent variables are ever and past-year use of alcohol, marijuana, and other drugs, as well as ever and past-year internalizing, externalizing, and substance use problems. 

   The first set of slides he presented indicate that youth who reported various tobacco product use were between four to seven times more likely to also report ever alcohol use. The results for marijuana indicate a six to nineteen fold increase in risk. The adjusted odds ratios for ever marijuana use according to ever tobacco use are quite striking: 14.6 for cigarettes, 9.7 for e-cigarettes, 18.9 for cigarillos and 13.2 for filtered cigars. The PATH study used the Global Appraisal of Individual Needs-Short Screener (GAIN-SS) to assess mental health issues and problems associated with substance use. This tool has subscales for substance use problems, internalizing problems such as anxiety and depression, and externalizing problems such as ADHD and conduct disorder-like symptoms. Each subscale is also categorized into no/low, moderate or high risk for mental health problem and/or a substance use problem. The proportions and odds of lifetime substance use problems according to ever tobacco use have very high adjusted odds ratios, 14.7 for cigarettes and approximately 8 for all other tobacco products. This is not causal substance use, it is substance use that is associated with symptoms of substance use disorders. Similar results were reported, with adjusted odds ratios ranging from one to two times the risk, for internalizing and externalizing problems according to ever tobacco use. 

   Dr. Conway proceeded with the results in progress for Wave 1 PATH study data in adults, which also accounted for sex differences. There is an overall estimated increase in risk, however, for females there is a higher risk for alcohol and marijuana use among certain tobacco product users, especially hookah and cigarillos. Although base rates are higher for males, the associations are much larger for females with traditional cigars, cigarillos, and filtered cigar use. As for substance use problems, internalizing problems and externalizing problems, the pattern is similar. Higher odds ratios for females relative to males and their association between tobacco use. 

   Wave 1 instruments and codebooks are available online at the Inter-University Consortium for Political and Social Research (ICPSR) and the National Addiction and HIV Data Archive Program (NAHDAP). In addition, restricted-use data files can be accessed via the Virtual Data Enclave (VDE) upon its approval. Public-use data files will be made available later in 2016. Dr. Conway ended his presentation by thanking NIDA staff that are members of the PATH Study, as well as the many field interviewers, participants, and students helping to collect and analyze the data. 

   Dr. Volkow and Council members thanked Dr. Conway for his presentation. Many council members commended the PATH Study and its members for the great work and looked forward to data that would help better understand causative association vs. correlation between substance use and mental health problems. Dr. Compton highlighted the extraordinary effort to make the restricted-use file available to the scientific community well before most of the papers had been written by the primary team.

8. Building the 4D Nucleome - John Satterlee, Ph.D., Acting Deputy Director, DNB, NIDA
   
   Dr. Satterlee began his presentation with a reminder that the human genome project started in 1990 and since then, there have been many projects such as the Roadmap Epigenomics Program, the ENCODE Program, the International Human Epigenome Consortium, among others that are working to understand the modifications on the DNA, the modifications of the proteins the DNA is wrapped around,, and the transcription factors that bind to DNA. The 4D Nucleome Program is the next layer to discovery. He then pointed to two slides that show the multitude of structures within the nucleus, as well as the chromosomal territories of a male cell that have all been discovered by the 4D Nucleome Program. The nucleome is defined as the organization of the nucleus in space and time (4D), in which nuclear organization is dynamic and continuously changing. These alterations of genome organization are associated with the development of cancer, premature aging syndromes, and learning and memory disorders. 

   He then showed a CRISPR image of the nuclear genome. This system can be used to test regulatory functions and image genetic elements dynamically in live cells. In addition, there are sequencing-based assays to gain physical interaction information such as which two pieces of the DNA are near each other within a nucleus. This allows the generation of maps of different cell types that suggest that the genome is organized in physically defined domains or loops. This in turn, provides information on connections between and within chromosomes. One way to visualize this information is by using a circus plot. This information is important because approximately 80% of disease-associated genetic variants reside in noncoding regulatory sequences with unknown targets. An example of that is the FTO gene, which was identified in a genome-wide association study for obesity. The FTO gene is expressed in the hypothalamus and by applying the Hi-C analysis, it was discovered that a variant within the intron FTO interacts with the transcription factor IRX3 that regulates white or brown adipocyte differentiation. 

   NIDA is interested in the 4D Nucleome Program because chromatin architecture is important in HIV infection. As described in a recent paper “Nuclear Architecture dictates HIV-1 integration site selection” by Marini et al. Nature, 2015. 521: 227-31, HIV prefers to integrate in transcriptionally active regions of the genome near nuclear pores; it avoids nuclear-lamina regions associated with inactive chromatin. Another paper by Clowney et al., Cell 2012; 151: 724-37 suggests that the mouse genome encodes 2200 different olfactory receptor alleles; however, only 1 out of 2199 olfactory alleles is expressed in a single olfactory neuron nucleus. By performing a pan-labeling experiment, one finds that 2199 inactive olfactory receptors are sequestered into subcellular structures within the nucleus. Furthermore, a partially NIDA funded study by Akbarian et al., at Mount Sinai looked at the NMDA glutamate receptor subunit. It appears that in these particular neurons conserved chromatin architecture regulates gene expression and cognition. He then provided one more example of recent studies that show a strong association between the 4D Nucleome Program and NIDA’s mission. Vogel-Ciernia et al., Nat Neuro 2013; 16:552-61 studied the BAF chromatin remodeling complex, as well as changes in DNA/nucleosome structure. The knockout BAF53b neuronal-specific subunit, was found to be required in hippocampus in adult neurons for long-term, but not short-term memory tasks, as well as for cocaine-associated memories and stabilizing long-term potentiation (LTP). 

   Dr. Satterlee then moved on to the current Common Fund 4D Nucleome Program. He reminded the audience that the Common Fund was established by Congress in 2008 with a budget of approximately $500 million annually to support transformative trans-NIH science. The 4D Nucleome Program is a trans-NIH project that receives a budget of approximately $25 million annually for five years, and has the following goals: To understand the principles underlying nuclear organization of mammalian genomes in space and time; the role that nuclear organization plays in gene expression and cellular function; and how changes in nuclear organization affect normal development and disease. The Program has several components to it: 1) Next Generation Tools to explore the relationship between genome organization and function. Within this component are multiple initiatives: study of nuclear bodies and components led by NIDA; nucleomics, which are maps that are a result of DNA sequencing analyses and assays; and imaging tools, such as the use of super resolution microscopy, soft x-ray tomography, and cryoelectron microscopy. 2) Reference maps of the 4D organization of the genome in a variety of human cells/tissues and cell states. The initiatives for this component include nuclear organization and function centers for technology development and data production; 4D Nucleome network data coordination and integration center to collect, store, curate and display data, metadata, and analysis tools to disseminate to the scientific community at large; and the 4D Nucleome network organizational hub to develop and maintain the 4DN portal, organize outreach activities, and coordinate the Opportunity Pool of funds.

   He added that the 4D Nucleome Program collaborates and has established U.S. and international partnerships. The program is approximately one year old, and thus it has not yet yielded progress reports. Dr. Satterlee welcomed the opportunity to return and update the Council members on the program’s progress in the near future. 

   Dr. Volkow and Council members thanked Dr. Satterlee for his presentation. Questions included whether or not the program would investigate pathological tissues, and look into the effects of radiation. Dr. Satterlee stated that at this current time, there isn’t sufficient evidence that these topics are being evaluated. 

9. National Institute of Neurological Disorders And Stroke (NINDS) Update - Walter Koroshetz, M.D., Director, NINDS, NIH

   Dr. Koroshetz began with an outline of discussion items he would cover in his presentation. He first spoke about the growing public, as well as scientific, interest in brain research. This is captured by trends in fields of study of trainees and fellows receiving Ph.D. degrees. The highest number of Ph.Ds. approximately 450, were in the field of neuroscience in 2013 compared with the second highest number of 275 in the field of health sciences. In addition, the highest amount of NIH funding of disease categories was for Neuroscience in 2015, and NIH support for Neuroscience extends across many Institutes and Centers (ICs). Multiple ICs are working together to advance neuroscience through the NIH Blueprint for Neuroscience Research. One of the trans-NIH Blueprint projects is the Connectome project whose goal is to understand the wiring connections of the brain using the best imaging tools. Another example is the Blueprint Neurotherapeutics project, which is a therapy development program that allows investigators access to commercialization expertise and contracts with pharmaceutical companies to conduct toxicology pharmacokinetics and pharmacodynamics (PK/PD) studies. 

   NINDS supports research across a wide disease spectrum, over 400 at this time. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. Some of the strategies that Dr. Koroshetz has put in place to meet the institute’s mission are to: invest across the full spectrum of basic, translational and clinical research; establish a data-driven process to identify unmet scientific opportunities and public health needs within and across neurological diseases; support research resources and technical advances that catalyze new discoveries; communicate and collaborate with the public and with others involved in biomedical research; train a robust and diverse neuroscience research workforce; and adopt a culture of evaluation and continuous improvement across all NINDS programs. He then went on to state that NINDS’ number of applications increased by 25 percent from 2010 to 2015, approximately 4000 applications, that includes complete Research Project Grant portfolio that has developed from Requests for Applications (RFA), Program Announcements (PA), and PAs that include specific set-aside funds. NINDS’ budget primarily supports disease-specific basic research, followed by basic, applied-translational, and applied-clinical research. 

   Recently, IC Directors across NIH met to address the concern that basic research grant applicants do not address public health relevance, especially related to clinical/human application. It was determined, and Dr. Collins recently published a paper in Science to back this, that the NIH recognizes and affirms the high impact basic research has on public health. If the research is strong and advances science, then it is relevant to public health. The second challenge has been enhancing reproducibility through rigor and transparency. NINDS has published guidelines on its website, as has the NIH, to improve training in qualitative and data mining analyses, with the goal of changing the culture of the new generation of scientists.

   In addition, NINDS has implemented a new funding mechanism to lessen the burden of grant application and writing on scientists. It is the NINDS Research Program Award (R35), which supports an awarded grant for a period of 8 years. The goal is to provide freedom for investigators to pursue longer range, innovative, or high-risk research; to reduce pressure to generate results quickly to achieve short-term goals; to allow investigators flexibility to follow up on serendipitous findings and explore new areas; and to reduce the amount of time spent on writing and administering multiple grant awards. NINDS will commit up to $20 million to support 20-30 awards. Another program that the IC is implementing is the NINDS Mentorship Award. The purpose of it is to reward outstanding mentorship, of pre- or postdocs, and incentivize good mentorship; to send a strong message that NINDS values good mentorship; to provide tangible reward for mentorship that will be understood by investigators, chairs and deans; and to provide additional support for excellent mentors that are doing excellent science so they can train additional trainees. 

   Dr. Koroshetz then moved on to NINDS’ and the National Institute on Aging’s (NIA) collaborative role in supporting Alzheimer’s Disease-Related Dementia (ADRD) research, where NINDS supports research on frontotemporal degeneration, Lewy body dementia, multiple etiology dementias, vascular contributions to cognitive impairment and dementia. Both institutes held an ADRD summit that was open to the public on March 29-30, 2016 to update the research recommendations. In addition, NINDS led, in conjunction with the Million Hearts, NIA and NHLBI the Mind Your Risks, a public education campaign to raise awareness among middle-aged people with hypertension that controlling blood pressure may decrease the risk for dementia, as well as stroke and also to provide scientific evidence for doctors who wish to discuss this topic with their patients. 

   He then moved on to the BRAIN Initiative, which stands for Brain Research through Advancing Innovative Neurotechnologies. The BRAIN Working Group report to the Advisory Committee to the NIH Director presented the following goals for its 2025 Scientific Vision: To focus on circuits and networks; to measure fluctuating electrical and chemical patterns within circuits; and to understand how all of this helps generate unique thoughts and actions. In 2014 the NIH BRAIN initiative awarded 58 applications $46 million. In 2015, it awarded 67 applications a total of $38 million that supported 131 investigators, including some in 8 countries outside of the United States. For fiscal year (FY) 2016, the BRAIN project has been appropriated $85 million, for a total of approximately $150 million since its inception. Dr. Koroshetz showed data that reflected the BRAIN portfolio by categories and funds. The majority of funds support human imaging/modulation, neural recording/modulation, and understanding circuits. Those are followed by cell/circuit tools, cell census, and training and dissemination. Although NIH does not know the FY17 budget at this time, the President’s budget recommended a $45 million increase to this initiative. 

   The BRAIN Initiative also has international partners, such as the Lundbeck Foundation, to develop a coordinated program to foster collaborative research in areas of mutual interest within the BRAIN Initiative. It jointly supports research projects involving Danish and U.S. scientists, and funds projects in Denmark. There are also similar partnerships between NIH and research organizations in Canada and Australia. Furthermore, multiple private organizations, such as the Howard Hughes Medical Institute, the Kavli Foundation, the Simons Foundation, and the Allen Institute for Brain Science have merged to form the Brain Initiative Alliance. The mission of this alliance is to coordinate and facilitate communications from its members related to the White House BRAIN Initiative. They have set up a website that serves as a single point of communication for all BRAIN Initiative-related announcements of funding opportunities and accomplishments. Dr. Koroshetz then showed the audience a slide representing the website’s home page and pointed out the different types of information it holds.

   Dr. Koroshetz provided examples of recent publications in respected peer reviewed journals that showcase the various exciting advances beginning to emerge from the BRAIN Initiative. He then went on to talk about the BRAIN Neuroethics Workgroup, which is a consultative ethics group that works with BRAIN leadership and investigators. It is co-chaired by Dr. Christine Grady and Hank Greely, and provides the following: Advice to NIH on neuroethics questions important for BRAIN that could be answered through focused empirical research; drafts relevant guidance documents to address critical ethical issues associated with BRAIN research; and considers proposed funding areas for BRAIN projects for questions of ethical risk. The Workgroup meets with BRAIN investigators that are conducting invasive human studies, and is part of a joint BRAIN/Blueprint neuroethics project team. 

   He then moved on to updates from other research topics important to NINDS. 1) Concussion research. Two neuropath studies are ongoing, and have published guidelines for pathologic diagnosis of Chronic Traumatic Encephalopathy (CTE); also NINDS-funded longitudinal study to characterize clinical syndrome of CTE from its appropriated budget. NINDS will form a working group of Council members to discuss next highest priority opportunities in concussion research. 2) Chronic Fatigue Syndrome (CFS), NINDS leads a trans-NIH Myalgic Encephalitis (ME) and CFS working group. Its goals are to advance research on the cause, prevention, diagnosis, pathophysiology, and treatment of ME/CFS; to communicate ME/CFS research information with ICs and NIH OD; and to organize the Federal Partners meeting to develop disease parameters, create new knowledge (diagnostics, epidemiologic studies, prognostics, causation), develop outcome measures, develop and test treatment, and to provide training and education opportunities. 

   NIDA, along with NINDS and other ICs sponsored the Marijuana and Cannabinoids: A Neuroscience Research Summit on March 22-23, 2016. The goal was to ensure that evidence-based information is available to inform practice and policy, particularly important at this time given the rapidly shifting landscape regarding the recreational and medicinal use of marijuana. 

   He then spoke about NINDS role in the Interagency Pain Research Coordinating Committee (IPRCC). In 2012 Assistant Secretary for Health at HHS tasked the IPRCC and the NIH to address the Institute of Medicine’s (IOM) recommendation to “develop a comprehensive, population health-level strategy for pain prevention, treatment, management, education, reimbursement, and research that includes specific goals, actions, time frames and resources.” This led to the National Pain Strategy, which is focused on the continuum of pain: pain as a temporal process, beginning with an acute phase that may progress to a chronic maladaptive state. NIDA will also be involved, and will transition the strategy from care-centered to a research one. 

   Dr. Koroshetz thanked Council and Dr. Volkow for the invitation to present. Many Council members and NIDA staff were interested in learning more about the R35 mechanism, as well the strategies used to implement rigor and reproducibility across NIH funded research. One council member commended NINDS’ effort with mentoring awards. 

10. There were no Public Comments

11. Adjourn

    The 123rd meeting of the National Advisory Council on Drug Abuse was adjourned at 3:10 p.m. 

Certification

I hereby certify that the foregoing minutes are accurate and complete.

Note: Informational materials provided to the public at the open session of the meeting may be obtained from the Executive Secretary.