Minutes of the 92nd Meeting of the National Advisory Council on Drug Abuse

February 7-8, 2006

The National Advisory Council on Drug Abuse convened its 92nd meeting at 3:00 p.m. on February 7, 2006 in Conference Room C, 6001 Executive Boulevard, Bethesda, Maryland. Dr. Nora D. Volkow, Director of NIDA, chaired the overall meeting and Dr. Timothy P. Condon, Deputy Director of NIDA, chaired the review of applications. The closed portion of the meeting on February 7, from 3:00 p.m. until 5:00 p.m. was for the purpose of reviewing applications for Federal grant assistance and was open only to Council members and Federal employees. The open session, which was open to the public, was February 8th, from 8:30 a.m. until 1:45 p.m. The Council adjourned on February 8, 2006 at 1:45 p.m.

Council Members Present:

Rodolfo Arredondo, Jr., Ed.D.
Steve Brasington, M.D. (Ex officio)
Jeanne Brooks-Gunn, Ph.D.
Mark T. Greenberg, Ph.D.
Dorothy K. Hatsukami, Ph.D.
Bankole A. Johnson, M.D., Ph.D.
Peter W. Kalivas, Ph.D.
Herbert D. Kleber, M.D.
Barry M. Lester, Ph.D.
Thomas E. Lucking, Ed.S.
Patricia I. Ordorica, M.D.
Linda J. Porrino, Ph.D.
John P. Rice, Ph.D.
Richard R. Suchinsky, M.D.
Claire E. Sterk, Ph.D.
David Vlahov, Ph.D.
Constance M. Weisner, Dr.P.H.
Nancy R. Zahniser, Ph.D.

Council Members Absent:

None

Council Chairs Present:

Nora D. Volkow, M.D.
Timothy Condon, Ph.D.

Executive Secretary:

Teresa Levitin, Ph.D.

Federal Employees Present:

National Institute on Drug Abuse, NIH, DHHS

Members of the Public Present:

Khursheed Asghar, Ph.D. - Contractor
Virginia Ashton - AACAP
Jack Blaine, M.D. - Contractor
Anne Bowen - MasiMax Resources, Inc.
Andrea Browing - Society for Research in Child Development
Sue Camaione - MasiMax Resources, Inc.
Bill Corrigall, Ph.D. - Contractor
William Dewey, Ph.D. - Univ. of Virginia Commonwealth
Julie Egermayer - COSSA
W.E. Ford - Synergy Enterprises
Stacia Hall - AACAP
Alyson Haywood - Madison Assoc.
Alexis Horan - American Society of Addiction Medicine
Andrew Kessler - NAADAC
Roxanne Kibben - Synergy Enterprises
Marian Kratage - MasiMax Resources, Inc.
Alan Kraut, Ph.D. - American Psychological Association
Kristin Kreager - AACAP
Joan Kub - JHU, School of Nursing
Mary Mayhew - Contractor
Geoffrey Mumford, Ph.D. - American Psychological Association
Michael Oxman, Ph.D. - Contractor
Patricia Pettinato - MasiMax Resources, Inc.
Darrel Regier, M.D. - American Psychiatric Association
Roy Walker - CSR, Inc.
Diedre Watkins - MasiMax Resources, Inc.
Jo Weekley - MasiMax Resources, Inc.
Lori Whitten - MasiMax Resources, Inc.
Joan Levy Zlotnik - Inst. for Advancement of Social Work Research
Patricia Zickler - NIDA Notes

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. Timothy Condon, Deputy Director, NIDA, called the meeting to order and welcomed the Council and staff. Dr. Condon provided an overview of the agenda for the meeting and 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. Teresa Levitin, 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 Office of Science Policy and Communications; the Division of Basic Neuroscience and Behavioral Research; the Division of Clinical Neuroscience and Behavioral Research; the 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.

   Members must absent themselves from the Council meetings during discussion of, and voting on, 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.

   For this Council, 766 applications, requesting $731,627,062 in Total Years Direct Costs, went to review. Of these, 283 were scored by the Scientific Review Groups (SRGs) representing $68,423,057 in First Year Direct Costs and $290,474,986 Total Years Direct Costs. Council concurred with the SRGs in time and amount. A request for one new MERIT was reviewed and approved. Council approved one administrative supplement. Council concurred with the IRG's recommendation on an appeal.

1. Call to Order

   Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order and welcomed the Council members. 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. Volkow called attention to future Council meetings.

2. Consideration of the Minutes of Council

   The Minutes of the September 2005 meeting were approved as written.

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

   Dr. Volkow presented information on the budget, what is new at NIH, recent NIDA activities, and science findings. For the budget update, she noted that for the 2006 appropriations from 2005 to 2006 there would be a total decrease of -.6 percent. Further, the 2007 President's budget indicates a further decrease of -.5 percent, which would bring NIDA to a total budget of $994,829.00.

   Dr. Volkow pointed to two new activities at NIH. One is a new investigators' program called the NIH Pathway to Independence Award Program. This program, announced in January of 2006, will provide an opportunity for promising post-doctoral scientists to receive both mentored and independent research support from the same award. Beginning in the fall of 2006, NIH plans to issue 150 - 200 awards per year for the next five years for this new program. NIH is committed to providing increased support for new investigators. Dr. Volkow also described the new NIH Office of Portfolio Analysis and Strategic Initiatives (OPASI). This new office will address the need for coordinated assessment and management of the overall portfolio of NIH-funded research. Dr. Volkow noted the need for transparent, systematic processes for coding specific diseases and conditions, assessing scientific opportunities and public health needs as well as integrating them into NIH-wide funding priorities, and coordinating funding of research areas that cut across or fall between the missions of individual institutes and centers. OPASI will be the NIH component that coordinates these activities, and it will help implement trans-NIH research. Dr. Volkow noted that there will be a common fund for shared needs in order for OPASI to fund initiatives that are in areas of interest to multiple ICs. Furthermore, current NIH Roadmap funds will serve as the baseline for the common fund.

   Dr. Volkow identified two active work groups composed of Council members and others. The first work group is the NIDA Basic Science Review Work Group which thus far has held one meeting in November of 2005 and will hold a second meeting in March 2006. This group has been charged with producing a report that will include a review of the current basic science program portfolio, recommendations to strengthen the current program, and suggestions for a five year plan for NIDA's basic science program. This work group will also examine the organization and management of the Division of Basic Neuroscience and Behavioral Research and its interactions with other NIDA divisions and centers.

   The second work group is NIDA's Approach to Grant-Making Work Group. The charge to this group is to produce a report recommending new actions or policies that might be needed to:

   < >ensure that, in this age of restricted budgets, young investigators are protected,ensure balance between large versus small science,consider guidelines regarding principal investigators with multiple grants or laboratories with multiple grants, andprovide ideas regarding the length and duration of grants.Steering Group Report - Peter W. Kalivas, Ph.D., Chair

   Dr. Kalivas identified the functions and members of the Steering Group. He noted that one of the functions is to work with NIDA staff to develop the Council agenda. Another function is to serve as the sounding board for the Director, providing suggestions and alternative solutions to immediate problems. Finally, the group brings concerns to the Director that have been expressed by Council members, grantees, or members of the scientific community.

   Dr. Kalivas brought two matters to Council's attention. First, he asked Council for their concurrence with a proposed addition to the National Advisory Council on Drug Abuse Guidelines for the Administration of Drugs to Human Subjects. Dr. Kalivas noted that studies which manipulate cue reactivity, which may mimic a drug effect, must ensure that the research participant is not discharged from the study in a heightened state of desire for drugs that would put the individual at risk of drug use or relapse. Council concurred with the recommended addition to Section IV of the Guidelines.

   Dr. Kalivas also noted that there had been a staff request to establish a Council AIDS work group. The purpose of that group would be to develop guidelines for NIDA sponsored investigators who are engaged in HIV prevention trials. Guidelines would ensure that proper ethical principles for protecting human participants were followed and that adequate care was provided after the trials were completed. This work group would also review and update, if needed, NIDA's 2001 policy on counseling and testing for HIV/AIDS and other infectious diseases. Council also concurred with this recommendation to establish a Council AIDS workgroup, and volunteers for that workgroup were sought from Council members.

4. Presentation of the NIDA Public Service Award - Nora D. Volkow, M.D., Director, NIDA

   Dr. Volkow presented the Institute's Public Service Award to Dr. William Dewey in recognition both of his pioneering vision in creating the Friends of the National Institute on Drug Abuse and of his outstanding leadership in raising public awareness about drug abuse and addiction research. She noted that Dr. Dewey has made important contributions in understanding the molecular mechanisms for reactions of opiates and cannabinoids. He has also played an extraordinarily important role in mentoring young investigators, and he has held important positions in professional organizations such as CPDD, the American Society for Pharmacology and Experimental Therapeutics, and the Federation of American Societies for Experimental Biology. Dr. Volkow stated that Dr. Dewey's vision and leadership in creating the Friends of NIDA has been of substantial importance, and she recognized and thanked him for his efforts. Dr. Dewey thanked Dr. Volkow and accepted the award on behalf of all of the people who are helping to make Friends of NIDA an effective organization. He noted that the goal of this organization is to end of the disease of drug abuse and that the only way this can be done is through the research agenda of the National Institute on Drug Abuse. Dr. Dewey described the organization and activities of Friends of NIDA, including Congressional briefings, and his vision for the future.

5. New Directions for OBSSR - David Abrams, Ph.D., Director, OBSSR, NIH

   Dr. Abrams described the role of the Office of Behavioral and Social Sciences Research (OBSSR). He noted that the mission of OBSSR is to increase the scope and support for behavioral and social sciences research, inform NIH and the scientific community about behavioral and social sciences research, represent to the NIH the value of such research, and disseminate information to NIH and the public.

   Dr. Abrams then described the nature of trans-disciplinary research, noting its levels of influence from the bio-behavioral to the aggregate/systems, where collective behavior is of interest. He noted that at the bio-behavioral level, one studies genes, proteins, cells, memory, mood, cognition, and behavior. At the aggregate level, where cluster and inter-individual variation is of interest, one looks at inter-personal nested contexts, and social and physical environmental factors.

   Trans-disciplinary science also takes into account life span development, including factors such as sensitive periods and phases, time varying and time invariant events, and other turning points. Dr. Abrams presented a complex chart identifying trans-disciplinary integration, noting both levels, time, and individual as well as group variation. Pathways transitions and trajectories all are taken into account with this complex model of trans-disciplinary integration.

   Dr. Abrams emphasized the importance of advancing the science of dissemination and putting what is known into practice. He pointed to the differences, as well as the connections, between translational research, dissemination research, and policy research, noting the importance of all of these ways of bringing what is known into practice.

   He then presented some of his research on tobacco use in order to illustrate various aspects of trans-disciplinary research. He noted that interventions must fit the level of causation. Thus, for example, primary and secondary prevention and treatment must be aimed at biological/genetic levels, while organization and community interventions should be aimed at the social positions levels.

   Dr. Abrams presented a chronic care model, identifying and integrating various levels of analysis from cells to society that need to be taken into account. He noted that the ultimate goal of trans- disciplinary research is to move from the molecular/cellular/individual and the molar/societal/ global into efficient and sustainable policy that will provide tailored and targeted interventions and policies based on biological, psychological, and socio-cultural research. Dr. Abrams noted that the RE-AIM model provides a way to elevate the science of dissemination and improve both basic and applied science in terms of looking at the mechanisms that would accelerate dissemination. The purposes of the RE-AIM model are to broaden criteria used to evaluate programs to include external validity and to evaluate issues relevant to program adoption and implementation, as well as to help close the gap between research studies and practice.

   Dr. Abrams also discussed translational research measurement standards. He noted the importance of focusing on early intervention, early detection and prevention as well as on acute disease. He also presented several examples from the tobacco area of successful prevention and dissemination work. Dr. Abrams noted that trans-disciplinary integration and dissemination is very challenging. After presenting data on various studies of tobacco, Dr. Abrams concluded that tobacco control has become a complex, adaptive environment and that systems approaches represent a major hope for substantial future change in health outcomes.

   Dr. Abrams also noted that he hoped OBSSR would help make the behavioral, social and public health sciences a common denominator for moving from disease management to prevention, moving from individual clinical work to large scale population work and using new technologies to yield better tailored and targeted interventions from the individual to the population level to the societal level.

6. Interactions Between Reward and Stress Systems - Marisela Morales, Ph.D., Intramural Research Program, NIDA

   Dr. Marisela Morales from the NIDA Intramural Research Program and the 2004 recipient of the Presidential Early Career Award for Scientists and Engineers presented some of her work on interactions between reward and stress systems. She is interested in the identification of neuronal pathways, neurons, and molecules involved in the biology of drugs of abuse.

   Dr. Morales noted that stress increases vulnerability to addictive drugs. Further, stressors reinstate drug seeking. She is particularly interested in investigating neuronal pathways, types of neurons, and molecules that might mediate functional interactions between stress and reward systems. Thus, she posed the question of whether or not corticotrophin-releasing factor (CRF) cells establish functional interactions (synapses) with cells located in the ventral tegmental area (VTA). Her answer to that was "yes". She also posed the question of whether CRF cells establish synapses with dopaminergic neurons in VTA. The answer to that was also "yes". The CRF system may activate directly the reward system because it is activating dopaminergic neurons in the VTA.

   Dr. Morales will continue investigations at the molecular level to see how CRF mediates its biological effects by interacting with different proteins. She hopes to identify which of the molecules she discussed mediates the functional interactions between CRF and VTA dopaminergic neurons. Dr. Morales then described her methods and some results and presented new data on questions about how, at the molecular level, CRF mediates its biological effects.

   Dr. Morales summarized her findings as follows: Within the VTA, the CRF axonal terminal establishes mainly asymmetrical (presumably excitatory) synapses with dopaminergic dendrites. The implications of this are that following stress, synaptical release of CRF in VTA may directly activate dopaminergic neurons, inducing release of dopamine within the mesocorticolimbic system. Further within the VTA, CRF-R1 and CRF-BP are preferentially expressed in dopaminergic neurons. The implications of this are that, at the cellular level, CRF may affect dopaminergic neurotransmission by interacting with CRF-R1 or CRF-BP located with VTA dopaminergic cell bodies.

   Dr. Morales suggested that CRF excited the synapses on dopaminergic dendrites. There may be a locus for the known interactions between stress mechanisms and the mesocorticolimbic dopamine system (a system implicated in addiction and a number of stress-related psychiatric syndromes) and comorbidity between the two. She concluded that these preliminary findings are important because they provide evidence indicating that stress systems may directly activate the reward system through CRF-R1 and CRF-BP. This suggests there may be new targets for medication development. Further, these results suggest several future studies that can unlock the complex relationships between reward and stress systems at the molecular and other levels, in order to better understand interactions between stress and reward systems.

7. CSR: Continuity and Change - Toni Scarpa, M.D., Ph.D., Director, CSR, NIH

   Dr. Scarpa spoke about the centrality of peer review, noting that peer review is the heart and soul of NIH. Further, peer review has produced an effective partnership between the federal government and research institutions, creating the best academic medical centers, the best biomedical/behavioral research and biotechnology, and has made possible the best cures and the best prevention for the public. The system of peer review at the NIH is admired and imitated here and abroad.

   Dr. Scarpa pointed out that there has been a substantial increase in the number of applications that were received by NIH and referred to CSR for review. For example, in 1998 CSR received about 40,000 applications. By 2005, that number had risen to nearly 80,000 applications. Dr. Scarpa briefly described review outcomes for NIDA applications that were reviewed in CSR.

   Dr. Scarpa noted that changes in CSR peer review operations are needed to increase communication between CSR, the ICs, reviewers, and applicants. Changes are also needed to increase uniformity, increase efficiency, and facilitate the work of IC program staff. Dr. Scarpa went on to describe several changes that are underway or planned. For example, he is interested in increasing communication and transparency, both within CSR and with NIH and other agencies, as well as with the scientific community.

   In order to increase uniformity, Dr. Scarpa has made changes in slate nominations, summary statements, and the use of unscoring. Specifically, he is encouraging study sections to unscore a full 50 percent of the applications that can be unscored. Other changes to increase efficiency include electronic submission and text fingerprinting as well as the use of artificial intelligence software.

   Dr. Scarpa elaborated on the potential of knowledge management tools for peer review to help CSR increase its efficiency. He noted that nine pilots are underway to begin to assess the benefits of knowledge management tools for peer review. He also documented several possible changes in CSR that will facilitate the work of IC program staff, including the use of sophisticated telephones so that IC staff can more easily participate in CSR meetings. He noted the plan to study one IRG every month, so that every two years there would be a full review of each IRG.

   Dr. Scarpa also intends to shorten the review cycle. He has taken initial steps to do so through the posting of summary statements earlier than was previously the case and through conducting a pilot study to speed the review process for new investigators so they will have time to revise and resubmit their applications for the next review cycle. This will be a savings of several months for these new investigators.

   Dr. Scarpa also described other possible changes in current systems, including addressing the concerns of some that clinical research is not properly evaluated and improving the assessment of innovative, high-risk/high-reward research. Also of importance is doing more to recruit and retain reviewers. Dr. Scarpa identified additional plans to expand the platforms for peer review and showed Council the number of applications reviewed for all of NIH, the number of research grant applications per applicant, and other data suggesting that changes are necessary to insure that peer review continues to operate efficiently and effectively and that the mission of CSR can be met.

   After a brief discussion of the CSR budget, Dr. Scarpa noted that CSR personnel do an extraordinary job in providing fair and thoughtful peer review and reminded Council that Scientific Review Administrators are absolutely essential to the NIH.

8. Update on the Blue Ribbon Services Task Force Report - Wilson Compton, M.D., M.P.H., Director, DESPR, NIDA

   Dr. Compton provided an update on the report of the Blue Ribbon Task Force on Health Services Research at the National Institute on Drug Abuse report. He noted that the charge of the task force was to develop recommendations about diffusion of research findings into practice, the utilization of the Clinical Trials Network as a platform for health services research, and the organization and leadership of health services research within NIDA and other federal agencies.

   Dr. Compton presented the names of the participants on this initiative. He then pointed out the responses NIDA has made, including a briefing for Dr. Zerhouni and a conference in Philadelphia on health services research. Other ways in which NIDA is addressing the recommendations of the task force include developing a clear understanding of what is meant by services research; increasing the portfolio on organizational, management, and financing; collaborating to develop standards for evidence based practices; and developing intra-and interagency collaborations.

   More specifically, he noted that, in defining health services research, one needed to understand that it is a multidisciplinary field of scientific inquiry. It is a field that examines how social factors, financing, organization, management, technologies, and individual factors affect access and utilization, quality of care, cost of care, as well as personal and public health and well being. These factors affect individuals, families, organizations, and institutions as well as communities and populations.

   Dr. Compton noted that enhancing research on organization, management, and economic issues was being met in several ways. For example, NIDA is collaborating with the Center for Substance Abuse Prevention (CSAP) on their National Strategic Prevention framework and is encouraging applications through the use of several program announcements.

   Dr. Compton presented findings from the organizational/management and the economics research portfolios. He then listed ways in which NIDA is working to develop standards for evidence-based practice. Dr. Compton addressed the intra-and interagency collaboration element of the report by pointing out that NIDA was using the CCTN and CJ-DATS, working with SAMSA and other partners on linking science to services, and braiding funding streams to maximize the efficiency and effectiveness of resources.

   The Task Force also provided recommendations about prevention services research, treatment services research, leading and managing services research at NIDA, and services research collaborations with the NIH and with external partners. Dr. Compton presented examples of how each of these areas is being developed in line with Task Force recommendations.

   The Task Force recommendations on leadership and management are being realized through a number of activities, such as communicating consistent and clear information on health services research at NIDA, integrating services research across divisions and branches, updating application review criteria and orienting IRG members, enhancing the dissemination of services findings and being proactive in developing proposal solicitations. Dr. Compton presented a comprehensive framework for implementation research that identified clinical practices, program components, and systemic factors, all of which are important to consider in implementation research.

   The Task Force recommendations on collaboration include a number of activities, such as developing and monitoring the services research agenda, improving technology transfer, developing standards for evidence based interventions, promoting and publicizing evidence based interventions, and improving methods for drug abuse services research. Dr. Compton also identified a number of researcher/practitioner collaborations, research-funded collaborations, and collaborative research processes that are taking place. He listed several co-sponsored RFAs and PAs as part of the collaborative research effort and noted that there are many challenges. These include budgetary constraints, entrenched bureaucracies, and personnel changes among collaborators.

   Dr. Compton concluded his presentation by noting that NIDA has been addressing all aspects of the Blue Ribbon Task Force Report on Health Services Research at the National Institute on Drug Abuse.

9. Adjournment

   The 92nd meeting of the National Advisory Council on Drug Abuse was adjourned at l:45 pm.

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.