Minutes of the 97th Meeting of the National Advisory Council on Drug Abuse

September 11-12, 2007

The National Advisory Council on Drug Abuse convened its 97th meeting at 3:00 p.m. on September 11, 2007 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 September 11, 2007, 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 September 12th, from 8:30 a.m. until 12:00 p.m. The Council adjourned on September 12, 2007 at 12:00 p.m.

Council Members Present:

Louis E. Baxter, M.D.
Warren K. Bickel, Ph.D.
Steve Brasington, M.D. (Ex officio) 
Debra K. DePrato, M.D.
Igor Grant, M.D.
Mark T. Greenberg, Ph.D.
Bankole A. Johnson, M.D., Ph.D.
Herbert D. Kleber, M.D.
Barry M. Lester, Ph.D.
Thomas E. Lucking, Ed.S.
Patricia I. Ordorica, M.D.
Daniele Piomelli, Ph.D.
Linda J. Porrino, Ph.D.
John P. Rice, Ph.D.
Mary Jane Rotheram-Borus, Ph.D.
Marina E. Wolf, Ph.D.
Janet Wood, M.B.A., M.Ed.
Xiaoyan Zhang, Ph.D.

Council Members Absent:

Ellie E. Schoenbaum, M.D.

Council Chairs Present:

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

Executive Secretary:

Teresa Levitin, Ph.D.

Federal Employees Present:

Members of the Public Present:

Pat Beauchemin - Therapeutic Communities of America
Anne Bowen - MasiMax Resources, Inc.
Andrea Browning - Society for Research in Child Development
Sue Camaione - MasiMax Resources, Inc.
William Corrigall, Ph.D.
Jessica Cotto, M.P.H.
Perry Fine, M.D. - American Academy of Pain Medicine
Stacia Hall - American Academy of Child and Adolescent Psychiatry
S. Jones, Ph.D. - University of Virginia
Marian Kratage - MasiMax Resources, Inc.
Sara Luster - SAIC
Meghan McGowan - Federation
Alan Moghul, Ph.D. - NASADAD
Geoff Mumford, Ph.D. - American Psychological Association
Amy Pollick, Ph.D. - Association for Psychological Science
Bobbie Peterson - RTI International
Pamela Pressley - Consortium of Social Science Associations
Keith Rivers, M.P.H. - Metropolitan Washington Council of Governments
Beth Staehle - MasiMax Resources, Inc.
H. Sweet - High Performance Tech, Inc.
Herb Weingartner, Ph.D.
Lori Whitten, Ph.D. - MasiMax Resources, Inc.
Joan Zlotnik, Ph.D., A.C.S.W. - Institute for the Advancement of Social Work

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, 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.

    

   For this Council, 1,055 applications, requesting $1,075,801,105 in Total Years Direct Costs, went to review. Of these, 364 were scored by the Scientific Review Groups (SRGs) representing $98,565,131 in First Year Direct Costs and $419,868,494 Total Years Direct Costs. Council concurred with the SRGs in time and amount.

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 May 2007 meeting were approved as written.

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

   Dr. Volkow began her Director's Report by noting the retirement of Mr. Richard Millstein, former Deputy Director of NIDA, and the resignation of Dr. Donald Vereen, former Special Assistant to the Director, and the arrival of Ms. Mary Affeldt as the new Associate Director of Management and Director of the Office of Planning and Resource Management. Dr. Volkow thanked Ms. Donna Jones, NIDA budget officer, for her generous assistance during the interim before Ms. Affeldt arrived. She also noted that Dr. Kenner Rice of the intramural program received the honor of the 2007 Smissman Award given by the American Chemical Society for his impact on the field of medicinal chemistry and that Dr. Anthony Fauci of NIAID received the extremely prestigious National Medal of Science from President Bush.

   Dr. Volkow then reported on the NIH and the NIDA budgets, noting that the actual NIDA 2006 budget reflected a decrease of -0.8% over the previous year and that the 2007 budget represented a 0.6% increase. The 2008 House and Senate budgets both reflected increases, though the President's budget was 0.0% for 2008.

   In addressing some of the new activities at NIH, Dr. Volkow described the epigenetics program that she is co-chairing. This program will have a number of research initiatives, including two for which NIDA is the lead institute: 1) the epigenomics data analysis and coordination center and 2) technology development in epigenetics. The epigenetics program, with its multiple RFAs and other activities, contains 10 years of work to provide a comprehensive understanding of epigenetics and its role in health.

   After describing the NIH Director's New Innovator Award, an announcement that brought in about 2,000 applications, and the status of changing NIDA's name to the National Institute on Diseases of Addiction, Dr. Volkow presented some data from the 2006 National Survey on Drug Use and Health on the use of specific illicit drugs among persons aged 12 or older. Of concern is the increase in the use of pain analgesics. Dr. Volkow pointed to some other interesting results.

   She then turned to activities at NIDA, beginning with a description of the NIDA Avant-Garde Award Program for HIV/AIDS research, noting that NIDA will provide approximately two to three awards of $500,000 in direct costs for up to five years for individuals intending to pursue innovative, high risk-high payoff research directions. This program will support individual scientists of exceptional creativity who propose approaches in the forefront of drug abuse and HIV/AIDS research.

   The CTN update included a summary of the number of trials completed and patients enrolled, among other information, and Dr. Volkow noted some of the issues and challenges in integrating HIV rapid testing and counseling into drug treatment in non-medical settings. She pointed out that there is a CTN protocol under development to evaluate the most effective strategy to ensure that persons in drug treatment programs are tested for HIV and receive their HIV test results. She stressed the importance of early testing and intervention in community treatment programs.

   Dr. Volkow then reported on several funding opportunities developed by the Division of Epidemiology, Services and Prevention Research (DESPR), including a program announcement on genetic epidemiology of substance use disorders and a request for applications for the Criminal Justice Drug Abuse Treatment Studies 2 Program (CJ-DATS 2). The recent activities of the Division of Clinical Neuroscience and Behavioral Research (DCNBR) include the development of an RFA (with DESPR) on brain imaging drug use prevention messages that brought in 16 applications. For the Division of Basic Neurosciences and Behavior Research (DBNBR), Dr. Volkow pointed to the important and risky initiative of identifying biomarkers for chronic exposure to drugs. A meeting was held to explore what new technologies might be of use in this area. A plan of action will be developed for this initiative, taking into account the recommendations that were made at this meeting. It was noted for the Division of Pharmacotherapies and Medical Consequences of Drug Abuse (DPMCDA) that a medications development scientific workgroup meeting took place May. This group recommended that NIDA pursue development of a cocaine vaccine and conduct a clinical trial to help prevent relapse during treatment of cocaine abusers and also investigate the development of a methamphetamine monoclonal antibody vaccine. Further, a meeting held in July on buprenorphine treatment for cocaine dependent patients recommended that NIDA initiate a pilot dose escalation study in an in-patient facility with cocaine-dependent subjects who have previous non-medical exposure to opioids and, depending on that pilot study results, design a clinical trial protocol of psychosocial treatment followed by buprenorphine treatment.

   The next major focus area for NIH Blueprint initiatives will be neuroplasticity, and a panel was convened in August to determine research needs and gaps. Solicitations for plasticity initiatives are anticipated for the summer of 2008. The Blueprint initiatives reflect the efforts of 14 institutes. NIDA is one of the largest participants, and more scientists from the NIDA community need to be involved in Blueprint activities.

   Recent NIDA activities have included -- and future activities will include -- a mini convention at the November Society for Neurosciences annual meeting in which outstanding scientists will present recent findings and discuss future directions in the neurobiology of drug abuse and addiction. In June, Dr. Volkow presented at the National Alliance for the Mentally Ill (NAMI) annual meeting on progress in understanding comorbidity. This was the first time a NIDA Director had been invited to speak at their plenary session. The Congressional Briefing sponsored by the Friends of NIDA was also described. Several ideas for increased NIDA/FDA collaboration and interaction were presented, and Dr. Volkow noted that FDA recently invited a number of drug abuse experts recommended by NIDA to become consultants and to serve on the Drug Abuse Subcommittee of the Drug Safety and Risk Management Advisory Committee.

   In addition to a TIME magazine issue that provided much information on how people become addicted, NIDA received the Governor's Award from the Academy of TV Arts and Sciences (the Emmy Award) for its very successful HBO series on addiction. This was a 14-part series that involved HBO, NIDA, NIAAA and the Robert Wood Johnson Foundation.

   Dr. Volkow concluded by presenting ideas from Council on the NIDA Dashboard: 1) how new investigators fare in obtaining their first R01 and how they fare in obtaining their first renewal, 2) how clinical and preclinical investigators compare in terms of success; 3) how more collaborations with other ICs might be encouraged and 4) how recruitment and training of medicinal chemists might be facilitated.

   Council thanked Dr. Volkow for her presentation and asked a number of questions, including whether it would be possible to more rigorously trace the substance abuse implications of new seroconversions; whether the meetings on biomarkers of chronic drug exposure have included experts in ethics, the law, and related areas; and whether comparisons between the success of new and experienced investigators included comparing the number of times each group had submitted an application and how much time had elapsed before funding. Dr. Volkow responded to this last point by stating that she would ask Dr. Norka Ruiz Bravo to see if this type of comparison could be done. There was also discussion on how the key role that addiction plays in HIV/AIDS needs to be better understood not only by the scientific community but also by the lay public. In answer to a question, Dr. Volkow noted that NIDA staff members are very active in providing technical assistance to investigators and she said that NIDA would explore comparing success rates for new and experienced investigators in terms of the number of applications and length of time it took from receipt to award. There was some discussion of the need for more medicinal chemists, with one Council member suggesting that something like the INVEST program might be considered. Also, the question of how best to assess the success of the clinical investigator was raised, since the measure of numbers of publications for preclinical investigators may not be the most appropriate metric for clinical investigators.

   Consideration of the unique pressures on clinical researchers led to a discussion of raising stipends for clinical researchers so that the stipends would better reflect the real salary of these clinicians and provide a greater incentive to participate in research. Dr. Volkow pointed to the success of NIDA's training grants when asked about retraining, training and cross-training efforts. Issues of how the CDC guidelines are viewed by the services community and the importance of the CTN protocol on HIV rapid testing for influencing practice nationally were noted. Dr. Volkow pointed to the care that was being taken in developing this initiative.

   Finally, Council returned to the issue of training of clinical investigators, noting that more investment in training clinical investigators through a variety of mechanisms needed to be considered. Council considered drafting a statement reflecting their concerns about training awards, including their concerns about salary for clinical investigators, and two Council members agreed to draft that statement for the full Council to discuss at the next meeting.

4. Update on NIH Peer Review Project - Jeremy Berg, Ph.D., Director, National institute of General Medical Sciences; Co-Chair, NIH Steering Committee Ad Hoc Working Group On Peer Revi

   Dr. Jeremy Berg described the multiple steps being taken as part of a comprehensive self-study by the NIH, in partnership with the scientific community, to strengthen peer review in changing times. Dr. Berg summarized the principles behind this study, noting that the increasing breadth, complexity, and interdisciplinary nature of the biomedical and behavioral sciences are creating new challenges for the NIH system and that peer review is a key component of this system. He pointed out that "system" is the key word, because the self-study is intended to explore every aspect of this system. He noted that NIH must not only continue to adapt to rapidly changing fields of science and ever-growing public health challenges but also work to ensure that the processes used to support science are as efficient and effective as possible for both applicants and reviewers, and the NIH must continue to engage the most talented reviewers.

   The approach to this study has included obtaining input from investigators, scientific societies, grantee institutions, voluntary health organizations and other members of the scientific community as well as input from NIH staff. Dr. Berg described the purpose and membership of two working groups, 1) an externally-focused one that is the working group of the Advisory Committee of the Director of the NIH (ACD) and is co-chaired by Drs. Keith Yamamoto of UCSF and Lawrence Tabak, Director, NIDCR, and 2) an internal one (a working group of the NIH Steering Committee) which is co-chaired by him and Dr. Tabak. This self-study is being conducted at the same time that CSR has launched several initiatives, some of which Dr. Berg mentioned, i.e., shortening the review cycle and the realignment of study sections. Overall, there are a number of activities going on simultaneously and several of them overlap. There is, moreover, a website that describes the various current and planned activities.

   Dr. Berg noted that there are three phases for this comprehensive self-study: 1) a diagnostic phase, 2) a pilot phase and 3) an implementation phase. As part of the diagnostic phase, NIH issued an RFI and created an interactive web site for soliciting opinions on how to enhance peer review. Specific questions were posed to encourage detailed responses, and more than 2,000 responses have been received. In addition, Dr. Zerhouni and the ACD working group co-chairs held two Dean's teleconferences which included about 100 participants, and the ACD working group is also holding a series of five regional town meetings and selecting a series of science liaisons to enhance out-reach to stakeholders. Further, the internal working group is soliciting information from the ICs about prior experiments and other relevant activities, and it also held three consultative meetings within NIH for staff and created a web-based survey for soliciting opinions. Additional efforts of the internal group include an analysis not only of relevant peer review literature but also of other agency approaches, including NSF and DOE, as well as the approaches of other countries. Also, the expert opinion of psychometricians will be sought in order to evaluate different models and approaches.

   The second phase will be that of piloting, in which the NIH leadership will consider input from the RFI and both working groups and will use this information and information from other sources to determine the next steps, including designing and initiating pilot studies and evaluating those pilots. Implementation is the third phase, and in this phase there will be the development of an implementation plan, and there will be briefings for NIH staff and councils, as well as scientific societies, the trade press, advocacy organizations and other relevant groups and individuals. Legislative briefings will also take place. Successful pilots will be expanded, and there will be the development of new peer review policies that will enhance the peer review structure and function.

   Dr. Berg then presented an array of emerging ideas, emphasizing that no idea had yet been accepted or endorsed and that all needed further consideration. These ideas encompassed a wide range of activities, including, for example, reviewing the project versus funding the person, providing retrospective versus prospective reviews, employing a virtual electronic applicant/reviewer dialogue to answer questions, employing a two-stage technical subject matter/editorial board model, scoring all new investigators, considering different types of review for different types of science such as clinical and interdisciplinary research, and using pre-applications to provide rapid identification and separation of competitive from non-competitive ideas. Some ideas were diametrically opposed to other ideas but all had been mentioned, often repeatedly, as ways to enhance the review system. He also noted a number of ideas concerning reviewers and review culture, such as more flexible service and other incentives for reviewers; ideas concerning scoring, such as binning and adding additional dimensions to extract more information; and other issues, all in the service of enhancing peer review.

   Council thanked Dr. Berg for his presentation and asked a number of questions. The first question was whether the relationship between score and publications was known, i.e. do those grants with the best scores eventually yield the most publications? Dr. Shurtleff noted that some preliminary analyses done for their division (DBNBR) did not show any correlation. There were also comments and questions about how applications are reviewed in other countries, about some of the ideas presented (though not endorsed), about the timetable, about the role of review and feedback to investigators, about ways to identify innovative applications and the response to the NIH Director's New Innovator Award Program. Dr. Berg again invited Council members both to provide input to this important process and to encourage others to do so.

5. Research, Condition and Disease Categorization: Background and Progress - Timothy Hays, Ph.D., Chief, Portfolio Analysis and Scientific Opportunities Branch, Office of Portfolio Analysis and Strategic Initiatives (OPASI), NIH

   Dr. Hays provided Council with information about a new way by which NIH-funded research will be categorized. He noted that every year NIH reports to Congress and the public on how much is spent on research and disease areas. Currently, Institutes provide categorization information to the Office of the Director, and funding on about 240 categories is submitted.

   However, a number of reports, including two reports from the National Academy of Sciences (1998 and 2003), have concluded that a better system of gathering and reporting NIH research on various topics and diseases is needed. Dr. Hays noted that now that applications are being submitted electronically, they can be more readily analyzed and categorized, and, over the last three years, his office has led the way, with scientific experts from across NIH, in trying out technologies, building definitions for categories, obtaining grant application information and engaging in other activities that will transform the process of categorizing the full NIH portfolio. Congress has now mandated the process in the NIH 2006 Reauthorization Act, and the new electronic system which will transform how NIH analyzes and reports its spending to Congress and the public in terms of categories of research areas and diseases is well underway.

   Dr. Hays noted that across the 27 relevant ICs there will be approximately 360 research and disease areas. The many benefits of this new system include consistency, transparency, efficiency and new opportunities for portfolio analysis. Thus, NIH will apply the same disease or research area definition to every single project it funds, and an exact project listing and dollar amount for every project will be available.

   Dr. Hays then briefly described how the new system works through his explanation of matching category and project fingerprints, noting that there is a thesaurus of over 300,000 medical concepts that are used in this system. He noted that the new methodology will be introduced to the public in the summer of 2008 and that in February of 2009 the results from the system with FY 2008 projects will be made publicly available. Dr. Hays concluded by providing his contact information and inviting Council questions.

   Council thanked Dr. Hays for his presentation and, in response to a question about NIDA collaborating with other Institutes, Dr. Hays stated that the system will allow identifying when NIDA has contributed to a project on which it is not the lead Institute.

6. Update on Genetics - Joni Rutter, Ph.D., Associate Director, Human Population and Applied Genetics, Division of Basic Neuroscience and Behavioral Research

   Dr. Joni Rutter noted that there are individual differences in vulnerability to addiction. Not everyone who takes drugs becomes addicted, but chronic exposure to drugs combined with a vulnerability phenotype leads to addiction. We are now able to examine genetic variants, or single nucleotide polymorphisms that contribute to addiction vulnerability. Dr. Rutter stated that the goal is to identify genetic contributions to drug abuse and that many approaches are needed, such as developing genome-wide association studies (GWAS), using low-density markers, and providing fine mapping and genotyping/resequencing opportunities. She then presented NIDA's approach to identifying genetic contributions to drug abuse. There are two main approaches: 1) trans-NIH initiatives, including leveraging ongoing work and participation in Roadmap, GAIN, GEI, and other programs and 2) trans-NIDA programs, including coordination among divisions and identification of supporting multidisciplinary/interdisciplinary research.

   Dr. Rutter described in more detail how NIDA is involved in trans-NIH human genetics activities. For example, NIDA is the lead institute on the Roadmap 1.5 effort in epigenomics and is involved with the pharmacogenetics research network (PGRN) to explore the effects of genes on responses to medicines. Other trans-NIH activities include the genetic association network (GAIN) and the genes, environment and health initiative (GEI).

   Within NIDA there is a coordinated effort through the genetics workgroup and the NIDA Genetics Coordinating Committee (NGCC) to foster a number of activities. The workgroup develops avenues of research, sponsors seminars and develops staff knowledge in areas of genetics research. The NGCC provides standards for data collection, data sharing and informed consent, evaluates the human genetics program, and recommends genetic application program assignments, among other activities. Dr. Rutter then presented a number of studies and findings in human genetics across NIDA and focused on converging genetics findings on nicotine, pointing to specific genes and gene variants.

   She concluded by describing the leadership roles of NIDA staff in trans-NIH involvement and the converging results of work within NIDA in human genetics that will inform treatment, prevention and intervention approaches as well as the announcements that have stimulated research and have demonstrated divisional coordination and programmatic synergy.

   - Jonathan Pollock, Ph.D., Branch Chief, Genetics and Molecular Neurobiology Research, Division of Basic Neuroscience and Behavioral Research

   Dr. Jonathan Pollock presented information on genetic model organisms, such as the mouse, which can provide clues to the genetic basis of complex diseases. He noted three different methods to identify gene function in mice: 1) haplotype associated mapping of natural variation in inbred strains; 2) selective breeding, and 3) induced mutations, i.e. knockouts. He pointed to the strengths of each of these methods, noting that, for example, inbred strains are a way to determine environmental effects through development across defined genotypes under controlled conditions, while selective breeding takes advantage of the mouse genome and gene variants (SNPs) among different mouse strains and knockouts, and transgenic animals are useful in identifying essential molecules in reward pathways mediating drug abuse and in separating cellular signaling pathways that mediate different phenomena associated with addiction.

   Dr. Pollock summarized some research approaches and findings associated with each of these three methods, including an NIH proposed project to increase genetic diversity in inbred recombinant mice, thereby making it possible to map any trait in the mouse. He briefly discussed translational genetic models of methamphetamine sensitivity, noting that differences in sensitivity are partially under genetic control in both mice and humans, and describing the effect of CSNK1E polymorphisms on response to methamphetamine. Dr. Pollock closed by presenting a summary of some global gene knockout programs and the NIH Knockout Mouse Project initiative to knockout 8000 genes in mouse embryonic stem cells in a C57BL/6 background.

   Council members thanked Drs. Rutter and Pollock for their presentations. They noted the importance of training investigators in this area and the importance of characterizing phenotypes in the environment. Also, the role of parasites was mentioned in the context of the importance of studying environmental exposures and how they might affect the genome.

7. Public Comments

   Joan Levy Zlotnik, the Executive Director of the Institute for the Advancement of Social Work Research, commented on the importance of training and supporting new investigators. She noted NIDA's substantial investment in funding seven interdisciplinary research development centers at schools of social work and the importance of evaluating this support.

8. Adjournment

   The 97th meeting of the National Advisory Council on Drug Abuse was adjourned at l2:00 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.