Minutes of the 99th Meeting of the National Advisory Council on Drug Abuse

May 13-14, 2008

The National Advisory Council on Drug Abuse convened its 99th meeting at 2:00 p.m. on May 13, 2008 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 May 13, 2008, from 2:00 p.m. until 4:30 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 May 13, 2008, from 8:30 a.m. until 12:30 p.m. The Council adjourned on May 13, 2008 at 12:30 p.m.

Council Members Present:

Louis E. Baxter, M.D.
Francisco Castellanos, M.D.
Steven Childers, Ph.D.
Thomas Crowley, M.D.
Debra K. DePrato, M.D.
Anita Everett, M.D.
Igor Grant, M.D.
Mark T. Greenberg, Ph.D.
Barry M. Lester, Ph.D.
John P. Rice, Ph.D.
Mary Jane Rotheram-Borus, Ph.D.
Ellie Schoenbaum, M.D.
Hazel Szeto, Ph.D., M.D.
Marina E. Wolf, Ph.D.
Janet Wood, MBA
Xiaoyan Zhang, Ph.D.

Council Members Absent:

Warren Bickel, Ph.D.
Daniele Piomelli, Ph.D.
Steve Brasington, MC

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:

Andrea Browning - Society for Research in Child Development
Shelley Caplan - IQ Solutions
Marshall Cohen
William Corrigall, Ph.D.
Susan David
Eric Davis - IQ Solutions
Diane Galloway, Ph.D. - Community Anti-Drug Coalition of America
Stacia Hall - American Academy of Child and Adolescent Psychiatry
David Kupfer - University of Pittsburgh
Geoff Mumford, Ph.D. - American Psychological Association
William Narrow - American Psychiatric Association
Pamela Pressley - Consortium of Social Science Association
Joan Zlotnik - Institute for the Advancement of Social Work Research

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, 941 applications, requesting $800,708,915 in Total Years Direct Costs, went to review. Of these, 487 were scored by the Scientific Review Groups (SRGs) representing $106,127,277 in First Year Direct Costs and $140,780,893 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: September 9-10, 2008; February 3-4, 2009, May 12-13, 2009, September 15-16, 2009; February 2-3, 2010, May 4-5, 2010, September 14-15, 2010.

2. Consideration of the Minutes of Council

   The Minutes of the February 2008 meeting were approved as written.

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

   Dr. Volkow began her report with a budget update, noting that the FY 2008 estimate was $1,000,700 for the Institute, a less than 1% increase from both the FY 2006 actual and FY 2007 budget authority dollars. She then described the NIH research initiatives stemming from the new NIH epigenetics initiative, noting that NIDA's lead responsibility for two of those initiatives. Dr. Volkow presented proposed Roadmap initiatives, including suggested ones in chronic pain, mitochondria, pharmacogenomics, tissue genetics and 3-D models of tissues.

   Recent NIDA activities have included the administrative review of Dr. Barry Hoffer and the intramural program. She noted that the Review Committee was very pleased with the work of Dr. Hoffer in the intramural program, and Dr. Volkow noted, in particular, Dr. Hoffer's mentoring skills. The NIDA draft Strategic Plan received 110 comments and recommendations from a wide variety of constituency groups and individuals. Some of the most salient topics addressed in the comments/recommendations included the areas of innovation in prevention research, strategies relating to HIV such as needle exchange, hepatitis C, opiate overdose, recovery, prescription drug abuse and research on treatment implementation. Based on these comments, NIDA has made changes throughout the document, added an introductory section, added a section on emerging issues and challenges and established a prevention workgroup including several Council members as well as experts in relevant areas. Dr. Volkow reminded Council that NIDA has moved its fellowships to CSR for review, as is the case for most ICs, and that NIDA will carefully monitor and evaluate this process.

   Dr. Volkow then turned to specific activities of the NIDA offices and divisions. She described the Avant-Garde award program for HIV/AIDS and drug abuse research, noting its purpose and review process and pointing out that the announcement had brought in more than 50 responsive applications across six scientific areas, with the largest areas being those of etiology/pathogenesis, therapeutics and behavioral/social sciences. Council will review these applications at the September 2008 meeting.

   The Division of Basic Neuroscience and Behavioral Research (DBNBR) has supported important research in genetics and it was recently reported in Nature that convergent results support CHRNA5/A3/B4 gene cluster association with nicotine dependence. This division recently supported a short course on the genetics and epigenetics of addiction that was extremely successful.

   The Division of Epidemiology, Services and Prevention Research (DESPR) is involved in launching a NIDA physical activity initiative for drug abuse prevention and treatment and there will be a meeting in June that raises the question of whether physical activity and exercise can prevent drug abuse. Further, the MTF study has shown that adolescents who exercise regularly had lower prevalence rates of legal and illegal drug use, though the causal relationships are not yet known. Finally, the Screening, Brief Intervention and Referral to Treatment (SBIRT) for Drug Abuse in General Medical Settings brought in 31 applications and there will be two SBIRT-related meetings in May, one on providing resources for clinicians for screening for drug abuse in general medical settings and a prescription drug abuse workshop. She noted the proactive role NIDA is taking in the engaging the general medical community and educating them on issues of drug use and abuse so that they will be better able to screen and provide brief interventions and appropriate referrals.

   The Center for the Clinical Trials Network (CCTN) has prepared a draft concept for a CTN SBIRT protocol which would be a study intended to address a critical knowledge gap identified by the U.S. Preventive Services Task Force: Does screening, when followed by appropriate intervention lead to improved outcomes? It is proposed to embed a behavioral healthcare expert in medical primary care settings and establish a liaison with community based addiction treatment programs in improving outcomes. It will also be useful to establish collaborations with the CTSAs for screening and brief interventions in the primary care setting. NIDA will be working with the Mayo Clinic CTSA. Further, the CTN will be collecting data on methamphetamine and other drug use in Tribal communities and on reservations in collaboration with American Indian and Alaska Native tribes and communities, and DESPR is supporting supplements relating to methamphetamine abuse in Native American populations.

   The Division of Clinical Neuroscience and Behavioral Research (DCNBR) sponsored an RFA on Facilitating Self-Control of Substance Abuse Related Brain Activity through Real-Time Monitoring of fMRI Signals that brought in 24 applications and the Division of Pharmacotherapies and Medical Consequences of Drug Abuse (DPMCDA) has sponsored research leading to interesting data on the effects of THC and Lofexidine in a human laboratory model of marijuana withdrawal and relapse.

   Dr. Volkow then described a number of workshops, conferences and other activities that had taken place recently or would take place in the near future, including the many presentations sponsored by NIDA at the May meeting of the American Psychiatric Association, a Congressional briefing on the genetics of drug abuse and addiction, Other activities include NIDA presenting awards for the first time for addiction science projects presented at the Intel International Science and Engineering Fair, the world's largest science competition for high school students. Three students will receive awards for exemplary projects in addiction science. The Blending Addiction Science and Treatment conference scheduled for June has already registered over 1100 participants, and NIDA is sponsoring a skills building workshop and a satellite symposium at the XVII International AIDS conference in Mexico City in August. Dr. Volkow also noted the symposia and workshops that NIDA was sponsoring at the annual meeting of the College on Problems of Drug Dependency (CPDD) and she described the participants and some of the activities of the NIH/Department of Energy nuclear medicine working group.

   Council thanked Dr. Volkow for her presentation and raised a number of points in response to that presentation. It was noted that a brief screening for drugs, alcohol and mental health together would be most efficient and that the Mayo Clinic and CTSA with which NIDA is working has unique resources that will be difficult to reproduce in other settings. Dr. Volkow noted that it is likely NIDA will partner with other CTSAs as well and that an integrated screening instrument is the goal and that we are working with NIAAA now. The importance of spreading NIH resources throughout the country was noted as was the importance of substance use being seen as a medical problem which people could honestly and openly report without worry of sanctions. The short course in genetics was praised as was the amount of material NIDA has developed for treatment providers. The need to disseminate clinically relevant research data as quickly as possible was noted and Dr. Volkow described some of NIDA's activities in this area. Policy change in Colorado on screening and treatment was described. There was some discussion of the need for more global as well as national data on the contribution of illicit substances to medical diseases, both chronic and acute.

4. DSM-V Research Conferences & Task Force Development: Past, Present and Future - Darrel A. Regier, M.D., M.P.H., Executive Director, American Psychiatric Institute For Research and Education; & Director, Division of Research American Psychiatric Association On Peer Revi

   Dr. Darrel Regier began his report on research planning for future psychiatric classifications by noting that NIMH, NIDA, and NIAAA had jointly supported the American Psychiatric Institute for Research and Education to review the research base for DSM-V and introducing two colleagues, Dr. David Kupfer and Dr. Charles O'Brien. Dr. Regier explained that he would provide information on the conference series that was supported by the cooperative agreement, that Dr. Kupfer would describe the third phase of the DSM development program, and that Dr. O'Brien would present information on the current state of the work group on substance use disorders.

   Dr. Regier then noted several perceived shortcomings in DSM-IV, including high rates of comorbidity and the use of the "not otherwise specified" category in both inpatient and outpatient services. He expressed the concern that the DSM might be hindering research progress. He noted pressures to go beyond reliability in classification by improving validity and moving toward an etiologically-based classification. He raised the question of whether there are data to assist in developing and refining diagnoses in the cognitive-behavioral sciences, family studies, molecular genetics, and neuroscience that can be helpful in developing/changing/refining diagnoses. The question then becomes whether research has advanced to the point where it can be usefully incorporated into the revision and evolution of classifications, moving beyond clinical consensus and building on empirical work.

   A multidisciplinary, international effort has been sought to engender these improvements and to provide careful planning for the DSM-V revision process. Plans for revisions were then described, including three initial work conferences and six white papers developed between 1999 and 2002, with identification of gaps that needed to be filled. The conference grant from NIH has led to further diagnosis-specific work to develop research agendas, and 13 conferences have been held over five years, with an additional aim of developing a unified DSM and ICD. The goal of promoting international collaboration among members of the scientific community and stimulating the empirical research needed to allow informed decision making regarding crucial diagnostic deficiencies identified in the current nosology is a complex one. To date, all 13 research planning conferences have been held, with 367 participants representing 39 countries, including 16 developing nations. Conference output has included the publication of papers in relevant peer-reviewed journals and special sessions at international forums. One of the four published monographs is on diagnostic issues in substance use disorders. Several other monographs are in press or preparation. Eighty-three journal articles have already been published from the conferences, since one goal is to publish as much as possible from the conferences in peer-reviewed journals. Dr. Regier briefly described the conference on substance use disorders held in February, 2005 and some of the research implications of that conference, including dimensional versus categorical approaches to classification and the use of term "addiction" versus "dependence" in the substance use disorders.

   Dr. Kupfer then reported on the next phase of activity. He noted the importance of basing recommendations on current research evidence and also stressed the importance of maintaining continuity with DSM-IV, introducing an interesting dialectic. The revision principles also include making optimization of clinical utility the highest priority in modifying DSM-V. Dr. Kupfer pointed to the importance of considering developmental trajectories across the life span and of thinking in dimensional, not simply categorical, terms. He also described the challenge of keeping the DSM up-to-date with relevant research as it unfolds so that the incorporation of new knowledge - risk factors, prodromes, prevention - can be taken into account. Thus, this needs to be seen as a living document. He noted that an important goal is to facilitate to the highest extent possible uniformity and harmonization between ICD-11 mental and behavioral disorders and DSM-V disorders and their definitions.

   Dr. Kupfer then described the initial list of tasks and activities, which included harmonizing the timeline of the DSM and ICD revision processes and considering both severity and disability/functioning as separate dimensions. The review and identification of broad/superordinate categories of diagnoses also needs to be considered. Dr. Kupfer noted the task force and work groups involved in this process and the different activities of each. The Council was provided a Web site for more information. Cross-cutting study groups have been established to review areas such as a life span developmental approaches and gender and cross-cultural issues. Possible validators for diagnostic groupings were also noted, including neural substrates and genetic and specific environmental risk factors, as well as biomarkers, temperamental antecedents, symptom similarity, course of illness, and treatment response, among others. Dr. Kupfer concluded by presenting the DSM-V timeline.

   Dr. O'Brien presented the membership of the substance use disorders work group, noting that Council member Dr. Thomas Crowley was the co-chair. He described the deliberative process, with the work group divided into small sub-committees that hold frequent teleconferences and present their findings to the full work group at meetings and conference calls. In reviewing DSM-IV, work group members are asking where it can be improved and what opportunities there are to move beyond behavioral criteria and use biomarkers. Issues currently under active discussion and research include the non-substance addictions of gambling, computer gaming, and other candidates still under discussion. Dr. O'Brien noted the chairs of the subgroups addressing these issues, such as cannabis withdrawal and biomarkers. As with the other speakers, Dr. O'Brien noted that changes and additions must be supported by evidence. He also noted that there may be field trials and stressed the time pressure involved in this effort. Dr. O'Brien closed by offering the possibility of presenting progress reports to Council.

   The Council thanked the presenters for their comprehensive review of this important activity. Questions were raised about the inclusion of compulsive overeating and it was noted that there will be interaction between the substance use disorders and the eating disorders work group on this topic. Dr. Regier described earlier field trials and noted that one issue will be to look at what the impact that some of the dimensional measures would have. It will be especially important to see what aspects of a diagnosis are constant across culture or gender. Comments and questions were also raised about the importance of stress-induced disorders, which are highly comorbid with substance abuse, smoking, and the complexity of separating and treating various comorbid conditions as well as ways in which a developmental approach can be taken. The possible relationship between conduct disorder and substance abuse and the challenges of developing a classification system that is relevant to medication selection were also noted. A caution was raised not to assume that everything is genetic or neurobiological, though these are certainly necessary factors in outcome. The Council again thanked Drs. Regier, Kupfer, and O'Brien.

5. The NIDA SBIR/STTR Program - Susan Weiss, Ph.D., Branch Chief, Science Policy Branch, NIDA

   Dr Weiss opened her presentation on the NIDA SBIR/STTR program by describing the difference between the SBIR and the STTR programs, noting that both these set-aside programs for small businesses have been reauthorized by Congress and extended to September 2008 (SBIR) and 2009 (STTR). The SBIR program began in 1982 and Congress designated four major goals of the SBIR, which are to stimulate technological innovation; use small business to meet federal R&D needs; foster and encourage participation by minorities and disadvantaged persons in technological innovation, and increase private-sector commercialization innovations derived from federal R&D. The major goals of the STTR, which began in 1992, are to stimulate and foster scientific and technological innovation through cooperative research and development carried out between small business concerns and research institutions as well as to foster technology transfer between small business concerns and research institutions. After noting some of the critical differences between the two programs, including the requirement for a research institution partner for the STTR and the requirement for the principal investigator of the SBIR to have at least 50% employment with a small business concern, Dr. Weiss then described the eligibility requirements for both programs and noted the three phases for both, i.e., Phase I of $100,000 and 6 months (SBIR) or 12 months (STTR) for the feasibility study; Phase II for the full research/R&D with $750,000 and a two-year award for both programs and Phase III, the commercialization stage that does not use SBIR/STTR funds. She noted that NIDA also supports Phase II competing continuations to provide additional research funds to move already identified drugs or devices requiring regulatory approval into clinical trials. She also described the SBIR "fast-track" program, which NIDA supports, that condenses the standard application, review and award process, allowing the investigator to apply for Phase I and Phase II support at the same time, and she noted the circumstances under which it would be a good option.

   Dr. Weiss then turned to the NIDA SBIR/STTR program, noting that the FY08 budget estimate was $15,500,000 for SBIR grants, $2,590,000 for STTR grants and $6,000,000 for SBIR contracts. She described the NIDA SBIR contract mechanism in more detail, noting that program staff submits contract solicitations which are reviewed in NIDA. About 10 solicitations are sent to NIH for inclusion in the NIH SBIR Contract Solicitation. At most, NIDA awards one contract/solicitation. Contract concepts have included science literacy materials, metabolomics technologies, marketing prevention interventions, epidemiological tools and electronic data capture for clinical trials.

   The success rates from FY02-07 for NIDA's SBIR and STTR programs were presented. In FY07, 78 applications for the SBIR were received and 29 were funded, while 18 STTR applications were received and 3 were funded in that same fiscal year. For FY07, NIDA achieved the second highest success rate for Phase I SBIRs among all the funding institutes but was below the NIH average in Phase II success rates.

   Dr. Weiss then described the types of SBIR/STTR projects that NIDA has funded. They include a variety of projects for different age groups, different problems and different products, ranging from a multimedia interactive version of the Addiction Severity Index (ASI) to a science club kit for elementary school children to nanoformulations for drug delivery. She presented examples of successful projects, including a clip from an award-winning documentary, a film called Euphoria, and an interactive multimedia version of the ASI, in which the person is able to enter his/her own data, which is then formatted and given to the treatment provider.

   Dr. Weiss concluded by noting that there is a web site with information about this program and that Dr. Cathrine Sasek is the NIDA coordinator for the SBIR/STTR program.

   Council members thanked Dr. Weiss for her presentation and asked about the proportion of grants that go from Phase I to Phase II and Phase II to Phase III and noted the importance of bringing knowledge to the stage of implementation. Dr. Sasek mentioned that NIH began a commercialization assistance program to help Phase II grantees move to the commercialization phase. She noted that this training program has been very successful. Council also raised the question of how drug development, with the basic science discovery of new molecules and new targets, had fared in this program. Dr. Condon and Dr. Volkow invited Council members to encourage colleagues to participate in these two programs.

6. Council Operating Procedures And Statement of Understanding - Teresa Levitin, Ph.D., Director, Office of Extramural Affairs, NIDA

   Dr. Levitin reminded the Council members that, on a yearly basis, they need to review and approve of the Council Operating Procedures and Statement of Understanding. Dr. Levitin noted that the current statement had already been sent to them and that, thus far, she had received no requests for changes in the delegation of authority or any other matter. As no questions or comments were raised, Dr. Levitin asked for approval, and the Council unanimously voted to approve the document as written.

7. Public Comments

   Dr. Virginia Anthony from the American Academy of Child and Adolescent Psychiatry congratulated Dr. Volkow on her five years of leadership of NIDA.

8. Adjournment

   The 99th meeting of the National Advisory Council on Drug Abuse was adjourned at l2:30 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.