Revised February 2014
September 4, 2013
The National Advisory Council on Drug Abuse convened its 115th meeting at 8:30 a.m. on September 4, 2013 in Conference Room C, 6001 Executive Boulevard, Bethesda, Maryland. The closed portion of the meeting on September 4, 2013, 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 September 4, 2013, began at 10:30 a.m. The Council adjourned on September 4, 2013 at 3:45 p.m.
Council Members Present
Regina Carelli, Ph.D.
Nabila El-Bassel, Ph.D., D.S.W.
Carl Hart, Ph.D.
James Hildreth, Ph.D., M.D.
Elizabeth Howell, M.D.
Terry Jernigan, Ph.D.
Thomas Kirk, Ph.D.
Robert Lenox, M.D.
Caryn Lerman, Ph.D.
Kelvin Lim, M.D.
Barbara Mason, Ph.D.
Linda Mayes, M.D.
Michael Nader, Ph.D.
Marina Picciotto, Ph.D.
John Rotrosen, M.D.
Jon-Kar Zubieta, Ph.D., M.D.
David Shurtleff, Ph.D., Acting
Mark Swieter, Ph.D., Acting
Federal Employees Present
Jane Acri, Ph.D.
Members of the Public Present
Yoshie Davison, M.S.W. - American Academy of Child and Adolescent Psychiatry (AACAP)
Arlene Deverman, CAE - American Society of Addiction Medicine (ASAM)
Donna Ferrari-American Association of Colleges of Osteopathic Medicine (AACOM)
Katia Howlett, Ph.D. - Synergy Enterprises, Inc.
Wayne Lindstrom, Ph.D. - Mental Health of America
Molly Mazuk - American Society of Addiction Medicine (ASAM)
Caroline Morton - Nova Research Company
Geoffrey K. Mumford, Ph.D. - American Psychology Association (APA)
Nancy Moy Yuen - SRI International
Emily Smith, M.P.H. - RTI International
Allie Unger - American Society of Addiction Medicine (ASAM)
Evelyn Yang, Ph.D. - Community Anti-Drug Coalitions of America
Closed Portion of the Meeting – September 4, 2013
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. Mark Swieter, Acting 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.
In turn, the Director or a designee for the Division of Basic Neuroscience and Behavioral Research, Division of Clinical Neuroscience and Behavioral Research, Division of Epidemiology, Services and Prevention Research, and the Division of Pharmacotherapies and Medical Consequences of Drug Abuse presented their applications for consideration by the Council. For each, Council provided concurrence with the initial scientific reviews en bloc. Council also approved two Method to Extend Research in Time (MERIT) awards. Administrative supplements were approved. Relevant applications were presented to Council for Special Council Review, and Council agreed with program assessments. All Trans-NIH Initiatives, i.e., Blueprint and Roadmap 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 – September 4, 2013
Call to Order
Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order. She 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. Dr. Shurtleff called attention to future Council meetings: February 4-5, 2014, May 6-7, 2014 and September 2-3, 2014.
Consideration of the Minutes of Council
The Minutes of the May 2013 meeting were approved as written.
NIDA Director’s Report - Nora Volkow, M.D., Director, NIDA
Dr. Volkow began her presentation with an update on the budget. She explained that although it is not yet clear what the budget will be for fiscal year 2014, NIDA will pursue a conservative approach to it. Turning to what is new at NIH, Dr. Volkow spoke about the new BRAIN Initiative, which has the support of the President and Dr. Collins. The aims of the initiative are to construct a dynamic picture of brain function that integrates neuronal and circuit activity over time and space, and to build on a growing scientific foundation in neuroscience, genetics, physics, engineering, informatics, nanoscience, chemistry, mathematics, etc. to catalyze an interdisciplinary effort of unprecedented scope. The initial year of funding of over $200 million will be provided by both government agencies and private organizations. Dr. Collins has selected an NIH Advisory Council to the Director BRAIN Working Group of experts in a wide array of neuroscience fields and charged it with articulating scientific goals and developing a plan including timetables, milestones, and costs. The BRAIN Working Group has been and will continue to seek broad input from the scientific community through open meetings and workshops, and it is to deliver an interim report on high-priority areas for FY14 funding in the summer of 2013 with a final report due in June 2014.
Dr. Volkow next spoke about recent increasing awareness in the scientific and lay communities of difficulties researchers have had in reproducing published results, particularly preclinical studies in the area of medications development. It is especially important that the preclinical basis be solid for clinical trials because they are expensive to conduct and impact public health. NIH is undertaking efforts to address this issue. A set of guidelines has been established that include raising community awareness, enhancing formal training of researchers in scientific methodologies, improving the evaluation of applications for scientific rigor by both peer review committees and NIH staff, protecting the integrity of science by partnering with journal publishers to adopt more systematic review processes for publications, and increasing stability for investigators. Toward this last guideline, Dr. Volkow spoke about NIH Common Fund Funding Opportunity Announcements that target the investigator rather than a specific research project, including Transformative R01, New Investigator DP2, Pioneer DP1, and Early Independence DP5.
Dr. Volkow then provided an update on the activities of the Collaborative Research on Addiction at NIH. NIDA, NIAAA and NCI continue to pursue ways to foster integrative approaches to research on addiction. In support of this aim, two FOAs were recently by the CRAN Institutes to provide supplements to existing grants for research into drug comorbidities.
Dr. Volkow next spoke about current activities at NIDA focused on expanding research on marijuana. As revealed by the 2012 National Survey on Drug Use and Health study and the Monitoring the Future study, there has been a recent significant increase in the consumption of marijuana in the US, while at the same time there has been diminished concern by US high schoolers about the harmful effects of marijuana. Taken in the context of the trend in states across the nation toward legalization of marijuana for medical purposes, NIDA is currently supporting research to identify the consequences and possible adverse effects of such policy changes in a variety of areas including patterns of drug use, education, and the criminal justice system. NIDA staff have also identified as urgent research needs about marijuana identified prospective studies in children and adolescents to evaluate the effects of marijuana exposure on brain development, characterization of the cannabinoids involved in marijuana’s effects, and treatment and prevention studies.
Dr. Volkow then announced the 2013 awardees of the NIDA Avant-Garde awards for HIV/AIDS research. Dr. Warner Green of the Gladstone Institutes will examine caspase 1 inhibitors to determine whether they can alter rates of CD4 T-cell loss and progression to AIDS. Dr. Richard Sutton of Yale University will identify genetic factors responsible for host control of HIV. Dr. Timothy Cardozo of NYU Langone Medical Center will work to produce a combined HIV and cocaine vaccine based on a common protein scaffold.
Council thanked Dr. Volkow for her presentation. One line of questions focused on working to expand the number of Institutes and Centers involved in functional integration to address complex questions such as how and to what extent exposure of children and adolescents to prescription medications and other risk factors in the home could impact developmental outcomes, and whether it would be possible to leverage already existing studies funded by NIH, private industry or other nations. Council also asked about the breadth of coverage by newly awarded administrative supplements to study the effects of changes in marijuana policy, and if there were plans to study the long term consequences of marijuana use during pregnancy on the children of those pregnancies. Other inquiries included whether NIDA or other ICs were able to fund research into compulsive behaviors other than drug and alcohol addiction, and if addiction recovery might be tracked through the addition of questions to the National Household Survey.
Addressing Viral Hepatitis in Drug Abusing Populations: Opportunities for Enhancing Outcomes - Ron Valdiserri, M.D., M.P.H., Deputy Assistant Secretary for Health Infectious Diseases & Director, Office HIV/AIDS and Infectious Disease Policy, DHHS
Dr. Valdiserri started his presentation discussing the many challenges that exist in addressing hepatitis C infection in drug abusing populations. Injection drug users are the primary carriers of HCV infection, although most who are infected don’t know that they carry the virus. The geographic and demographic extents of the incidence are unknown as there are insufficient funds for tracking viral hepatitis. According to the US Centers for Disease Control and Prevention, it is estimated that over three million Americans are infected with HCV and the estimated number of new cases each year is more than 16,000. Studies suggest that the number of deaths from HCV has recently surpassed that from HIV infection. Adding complexity the problem is an evolving trend in which people in their twenties convert from prescription opiate use/abuse to injecting heroin, probably due to the lower cost of heroin and the increasing difficulty in acquiring prescription opiates. Thus, HCV infection is under-diagnosed, under-reported and under-treated and represents a significant public health concern.
Dr. Valdeserri went on to describe actions taken by the US Department of Health and Human Services in this area including issuance of the Viral Hepatitis Action Plan in 2011, a major focus of which is to improve testing, care, and treatment of viral hepatitis. The Action Plan is being updated with goals for 2020, which include increasing from 45% to 66% the proportion of persons who are aware of their HCV infection and reducing by 25% the number of new HCV infections.
Dr. Valdeserri then spoke about a meeting convened by HHS in February of hepatitis experts to address the issue of combating viral hepatitis. One of the major highlights of the meeting was that because of its robust viability, HCV seems to be spread not only through sharing of needles and syringes among injection drug users, but also through the sharing of other drug paraphernalia such as cookers, filtration cotton, and rinse water. Other important highlights of the meeting included evidence suggesting that ,since most HCV seropositive individuals also carry HIV, treating both diseases at the same time can lead to better health outcomes, although work needs to be done to sort out the effective medications and doses to administer. Also, a few studies suggested that once in treatment for HCV, most study subjects adhered to the treatment. Additional studies showed the value of treatment as prevention in that successful treatment of HCV infections lowers the incidence of downstream liver diseases that come about as a result of not treating HCV infection.
Several recommendations for future directions came out of the meeting. There needs to be better definition of the scope of the problem (epidemiological research) and ways need to be developed to identify and reach young persons who have not yet transitioned from oral to injection opioid use. Developmentally appropriate HCV treatment services should be established. Longitudinal cohort studies of young injection drug users would better define HCV re-infection risk. Additional research on transmission risks associated with sharing drug preparation equipment and environmental contamination are essential. Health services research that identifies successful models to integrate HCV treatment into substance abuse treatment would be useful. It would be desirable to develop and test combination approaches (biomedical, behavioral, and structural). Better models of treatment as prevention for HCV among young injection drug users would reduce the related morbidity and mortality. And last, it would be a major accomplishment if a safe and effective vaccine for HCV were developed.
Council thanked Dr. Valdiserri for his presentation. Questions were asked about whether HHS intended to involve a strategy for HCV similar to the Seek, Test and Treat approach that has worked well with reducing HIV transmission, whether HHS would be able to provide funding for epidemiological studies, which are costly, and whether HHS would promote HCV testing for older individuals who may represent a reservoir of asymptomatic HCV carriers.
Collaborative Research on Addiction At NIH (CRAN): an Update - Susan Weiss, Ph.D., Associate Director for Scientific Affairs, Office of the Director, NIDA
Dr. Weiss explained that the mission of CRAN is to provide a strong collaborative framework to enable NIAAA, NIDA, and NCI to integrate resources and expertise to advance substance use, abuse and addiction science research and public health outcomes. She described the recent formation of a CRAN coordinating committee, which includes representation from NIDA, NIAAA, and NCI, that is working to coordinate the various activities that will be part of the functional integration CRAN represents. The coordinating committee has met regularly to discuss new funding opportunity announcements for FY14 and FY15, the development of a website, the upcoming Joint Council Meeting, and other short and long-term considerations related to CRAN, for example, training.
Dr. Weiss described CRAN-related FOAs for FY13. They included two RFAs, one with NIDA as the lead Institute on Prevention and Health Promotion Interventions to Prevent Alcohol and Other Drug Abuse and Associated Physical and Psychological Health Problems in U.S. Military Personnel, Veterans and their Families, and the second RFA with NIAAA as the lead Institute on Research on Comparative Effectiveness and Implementation of HIV/AIDS and Alcohol Interventions. CRAN FOAs for FY14 include two aimed at providing supplements to existing grants, one for competitive supplements, the other for administrative supplements.
CRAN-related Program Announcements are also being supported including Mechanisms of Alcohol and Nicotine Co-Addiction; Health Services and Economic Research on the Prevention and Treatment of Drug, Alcohol, and Tobacco Abuse; and Mechanisms of Alcohol and Stimulant Co-Addiction.
Council thanked Dr. Weiss for her presentation. There were questions about barriers to progress among the involved Institutes, plans for developing integrated training programs for predoctoral and postdoctoral fellows, and the absence of other Institutes such as NIMH in CRAN activities..
Crossing the Rubicon: NIDA/Industry Partnerships - Phil Skolnick, Ph.D., D. Sc. (hon.), Director, Division of Pharmacotherapies and Medical Consequences of Drug Abuse, NIDA
Dr. Skolnick began his presentation by showing a recent announcement in a trade journal that Teva Pharmaceutical Industries announced it was starting a Phase II clinical trial of an albuminated compound to treat cocaine addiction. He explained that this is highly significant since it marks the first time that a large pharmaceutical company has entered the field of cocaine use disorders. Moreover, if the trials are positive, Teva has the wherewithal, without any additional support, to take these trials to completion, to an NDA, after that, to manufacture it, to distribute it, to sell it, and to market it. This would guarantee that the medication would reach the largest number of patients.
Dr. Skolnick went on to explain that Teva and other pharmaceutical companies have recently begun partnering with NIDA for a number of reasons. One reason is that substance use disorders represent a “rescue” indication for drugs in the psychiatric portfolio. Although over the last five years pharmaceutical companies have either left psychiatry research or severely curtailed their programs, they now see advantage in trying to repurpose drugs they developed as treatments for addiction. A second reason for recent interest in partnering with NIDA is the demonstration by NIDA and others that treatments for substance use disorders could be highly profitable because the estimated large number of users of cocaine and other drugs represent a sizable market potential.
Dr. Skolnick also identified collaborations with AstraZeneca to test compounds to treat multiple types of substance use disorders, and he identified collaborations with several small pharmaceutical companies as well such as with Biotie to test nepicastat for cocaine dependence, with Lightlake Therapeutics to test medications to treat opiate overdose, with US Worldmeds to test lofexidine for opiate addiction, and Savant HWP to test 18-methoxycoronaridine for drug addiction.
Council thanked Dr. Skolnick for his presentation and acknowledged the remarkable success he and his staff were having in partnering with the pharmaceutical industry to develop medications for substance use disorders. Questions focused on the possibility that effective pharmacotherapy may involve giving patients multiple medications and the likely difficulties in getting companies to agree to test their compounds with those of other companies in clinical trials.
The DCNBR Research Portfolio - an Update - Joseph Frascella, Ph.D., Director, Division of Clinical Neuroscience and Behavioral Research, NIDA
Dr. Frascella started his presentation with an overview of how DCNBR is structured and which staff are in each of the components. He also added that the Women & Sex/Gender Differences Research Program and staff had recently become part of DCNBR. He then spoke about each component individually, its goals/missions and identified some key initiatives undertaken by each. The Women & Sex/Gender Differences Research Program funds travel awardees to the annual College on Problems of Drug Dependence meeting for junior investigators who are doing research in women and sex/gender differences. This year, the Program also spearheaded efforts by NIDA funded scientists to compete for administrative supplements on women & sex/gender differences from NIH. NIH intended to fund at least one supplement for each of 21 Institutes and Centers whose grantees applied; six NIDA-funded researchers received supplements.
Dr. Frascella reported that the Clinical Neuroscience Branch has supported research into the effects of acute and chronic drug administration; biological risk factors (genetics, personality, brain dysfunction); normative function related to substance abuse (reinforcement learning; cognition; decision-making, brain and genetic factors); translation of preclinical discoveries to human research, human pain research; neurobiology of HIV/AIDS, and training and promotion of career development (I/START, Blueprint Neuroimaging T90/R90, K’s, and T’s). He then spoke of future research, which is expected to be focused on such topics as temporal course of recovery of brain and behavioral dysfunction during abstinence; behavioral & biological markers that predict a variety of clinical outcomes including vulnerability, continued abstinence, treatment outcome, or relapse, and pain and response to analgesics; individual differences; new methods and approaches in areas such as behavioral/cognitive paradigms, regional brain interventions, complex and dynamic systems, the Connectome, the BRAIN Initiative; Big Data; increases in cannabis usage; and extension, validation, and replication of discoveries.
Dr. Frascella then spoke about the Behavioral and Integrative Treatment Branch that has as its major goals of this branch to produce effective and ultimately community friendly behavioral treatments for drug abuse and addiction in youth, adolescents and adults; determine the best ways to promote medication adherence for HIV and drug abuse treatments; and determine the best ways to treat pain. Future directions include identifying neurobehavioral targets/mechanisms of efficacious treatments to identify critical components; enhancing the ability to implement of treatments by incorporating technology, making treatments less-costly, and developing therapist training materials; increasing the link between neuroscience and treatment development to improve the potency of treatment; supporting research aimed at improving treatment of patients with psychiatric comorbidities (e.g., smokers with schizophrenia); and using medications to boost effects of behavioral treatment (i.e., cognitive enhancers).
Dr. Frascella talked next about the Behavioral and Brain Development Branch, which focuses on translational research to understand the sensitive periods of behavioral and brain development for risk and resilience for drug abuse. Some of the focus areas are the human brain and development, looking at cognitive and social neuroscience risks, integrating neuroscience and behavior for increasing efficacy of prevention and development interventions, environment and drug exposure, looking at prenatal, postnatal and adolescent exposure, HIV, comorbidity, and marijuana and harm to youth.
Council thanked Dr. Frascella for a comprehensive look at DCNBR’s research portfolio and future plans. Questions focused on whether there might be opportunities to partner with industry in the development of neurotherapeutics and some new imaging technologies and whether the new imaging technologies might be useful tools to use in clinical trials.
Improve Reproducibility of Research Research - Elena Koustova, Ph.D., M.B.A., Director, Office of Translational Initiatives and Program Innovations, Office of the Director, NIDA
Dr. Koustova began her presentation explaining that the ability to translate preclinical research into clinical success has been remarkably low. Evidence compiled over the past few years has suggested that the lack of reproducibility of preclinical studies upon which clinical trials are based may be a major factor. This has become a matter of increasing concern both within the pharmaceutical industry and at NIH as the costs of drug development have increased along with the number of late-stage clinical-trial failures, while at the same time demand for more effective therapies has increased. Failure to repeat published findings in clinical trials puts biotech companies out of business, diminishes venture capitalist willingness to invest in early stage clinical research and to fund academic spin-offs, wastes limited research funding, and erodes public support for research.
Dr. Koustova went on to explain that recent attention at NIH has focused on addressing these issues. A set of guiding principles has been developed that include raising community awareness to the problems, enhance formal training of researchers in experimental design and methodologies, improve the process by which grant applications are evaluated, protect the integrity of science by adopting more systematic review processes, and increase stability for investigators.
Dr. Koustova then described NIDA’s efforts to address the issue. Toward raising community awareness, NIDA will issue a Notice in the NIH Guide affirming NIDA’s commitment to research reproducibility and alerting the research community of additional steps to be taken. NIDA will include relevant language from the Notice in new Funding Opportunity Announcements it publishes. NIDA’s Office of Translational Initiatives and Program Innovations along with NIDA’s Office of Extramural Affairs will develop workshops for upcoming scientific meetings (e.g., College on Problems of Drug Dependence; Society for Neuroscience) to alert the drug abuse and addiction research community on the issues and NIDA’s efforts to address them. NIDA Director’s blog on this topic will be disseminated by various social media channels (e.g., Facebook, Twitter). And NIDA will solicit feedback from the research community, including from the National Advisory Council on Drug Abuse.
Toward enhancing formal training, NIDA plans to integrate modules and/or courses on experimental design into existing required training courses and into grant award terms and conditions. Toward improving the evaluation of applications, NIDA intends to use guidelines and checklists to systematically evaluate grant applications. Toward more systematic review processes, NIDA will collaborate further with scientific journals and the scientific community on efforts to improve rigor, including inviting journal publishers to workshops hosted by NIDA such as at the College on Problems of Drug Dependence, and partnering with them to improve research reproducibility. NIDA will also consider funding replication/reproducibility studies or centers. And toward the goal of increasing stability for investigators, NIH is considering relieving pressure on investigators to publish in the highest profile scientific journals by adapting the NIH biosketch to allow investigators to place their work into a functional context.
Council thanked Dr. Koustova for her excellent presentation and expressed support for the efforts NIH and NIDA were making to address the issue of research reproducibility. Suggestions were made to support the involvement of statisticians in analyzing research results as a standard practice and to require training grants and fellowships train fellows in proper research methods. Council also commented on the importance of NIH and NIDA trying to manage what were expressed major cultural shifts including training of researchers in proper scientific methods and statistical analyses, convincing journals to be actively involved in publishing well described experiments and all findings including negative findings, and influencing the process of academic advancement by changing the focus from quantity of research and publishing in high profile journals to quality of research contributions to science.
There were no Public Comments
The 115th meeting of the National Advisory Council on Drug Abuse was adjourned at 3:45 p.m.
I hereby certify that the foregoing minutes are accurate and complete.
Nora D. Volkow, M.D.
National Advisory Council on Drug Abuse
Mark Swieter, Ph.D.
Executive Secretary, Acting
National Advisory Council on Drug Abuse
Note: Informational materials provided to the public at the open session of the meeting may be obtained from the Executive Secretary.