105th Meeting Minutes

May 5, 2010

The National Advisory Council on Drug Abuse convened its 105th meeting at 8:30 a.m. on May 5, 2010 in Conference Room C, 6001 Executive Boulevard, Bethesda, Maryland. Dr. Nora D. Volkow, Director, NIDA, chaired the meeting. The closed portion of the meeting on May 5, 2010, from 8:30 a.m. until 10:30 a.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 5, 2010 from 10:30 a.m. until 1:30 p.m. The Council adjourned on May 5, 2010 at 1:30 p.m.

Council Members Present:
John P. Allen, Ph.D., MPA
Francisco X. Castellanos, M.D.
Steven R. Childers, Ph.D.
Debra K. DePrato, M.D.
Anita S. Everett, M.D.
Igor Grant, M.D.
Caryn E. Lerman, Ph.D.
Eric Nestler, Ph.D., M.D.
Daniele Piomelli, Ph.D.
Mary Jane Rotheram-Borus, Ph.D.
James L. Sorensen, Ph.D.
R. Dale Walker, M.D.
Xiaoyan Zhang, Ph.D.
Jon-Kar Zubieta, M.D.

Council Members Absent:
Louis E. Baxter, M.D.
Thomas J. Crowley, M.D.
Hazel H. Szeto, Ph.D., M.D.
Steven M. Wolinsky, M.D.

Council Chairs Present:
Nora D. Volkow, M.D.

Executive Secretary:
Teresa Levitin, Ph.D.

Federal Employees Present:

Members of the Public Present:
Llewellyn Cornelius, Ph.D. - Society for Social Work & Research
William Corrigall, Ph.D.
Christopher DaCosta, B.S. - PPD, Inc.
Susan David, Ph.D.
Meena Karithanom, M.P.H.
Julie Miller, Ph.D. - RTI
Amy Pollick, Ph.D. - Association for Psychological Science
Patricia President - MLS CSR, Inc.

Closed Portion of the Meeting - May 5, 2010

1. Call to Order

   This portion of the meeting was closed to the public in accordance with sections 552b(c) (4) and 552b(c) (6), Title 5, U.S. Code and section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2).

   Dr. Nora Volkow, Director, NIDA, called the meeting to order and welcomed the Council and staff, 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 Division of Epidemiology, Services and Prevention Research; the Division of Pharmacotherapies and Medical Consequences of Drug Abuse; the Division of Basic Neuroscience and Behavioral Research; the Division of Clinical Neuroscience and Behavioral Research; the Office of Science Policy and Communications; and the American Recovery and Reinvestment Act presented their applications for consideration by the Council. For each, Council provided concurrence with the initial scientific reviews en bloc. Council also approved all administrative supplement requests presented.

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

Open Portion of the Meeting - May 5, 2010

1. Call to Order

   Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order and introduced new 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 14-15, 2010; February 1-2, 2011, May 10-11, 2011, September 13-14, 2011.

2. Consideration of the Minutes of Council

   The Minutes of the February 2010 meeting were approved as written.

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

   Dr. Volkow began her report by providing an update of the budget. She noted that the 2011 President's Budget proposed a 3.3% increase over the previous year, which would bring NIDA's total budget to $1,094,048.

   Under the heading of "What's New at NIH" she addressed the status of the potential merger with NIAAA, noting that the full Scientific Management Review Board (SMRB) met March 10 and that the consensus was that some change is desirable. However, there was no consensus on whether that change should be structural or functional in nature. Specific recommendations are anticipated at the next full SMRB meeting later in May. Dr. Volkow listed three Recovery Act Limited Competitions, one to promote diversity in the scientific workforce, another for global health research, and another for global health innovations and training. She noted that the Health Care Reform Act contains new legislation that specifically tasks the NIH with playing a key role in the development of "high speed cures." She further noted a shifting paradigm for drug development research. That is, there is growing pressure on the pharmaceutical industry to increase the number and quality of cost effective new medicines without unsustainable R&D risks and costs and that there is a proposed alternative paradigm to the traditional drug development paradigm called "quick win-fast fail" that is of widespread interest. The goal and objectives of the Cures Acceleration Network (CAN) were briefly described. The goal is to dramatically advance development of new treatments and cures for debilitating and life threatening diseases by reducing barriers between laboratory discoveries and clinical trials.

   Recent NIDA activities have included the successful recruitment of Dr. Antonello Bonci to be the new Director of the Intramural Research Program. Dr. Bonci had been at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco. Dr. Volkow then presented the timelines and current accomplishments of the PDP, noting that this NIDA public/private partnership task force was established in November 2009 and submitted its concept paper for comments to the NIH PPPP in March of this year. There have been 10 responses to the Request for Information to identify organizations with the appropriate expertise to participate in a collaborative drug development partnership. Dr. Volkow noted that nine pre-applications had been received for the NIDA Translational Avant-Garde award program for medication development for diseases of addiction.

   Turning to the Division of Pharmacotherapies & Medical Consequences of Drug Abuse, Dr. Volkow introduced an excerpt from the NIH Director's testimony at the House Appropriations Hearing on April 28 in which someone who had smoked for 25 years and was unable to quit finally succeeded in quitting through participation in a Phase II clinical trial of an anti-nicotine vaccine called NicVAX. A clinical trial of NicVAX is now underway using NIH Recovery Act funds for the first Phase III trial of a smoking cessation vaccine. Dr. Volkow then summarized data and several potential targets for medications development and described two RFAs, "Medications Development for Cannabis-Related Disorders" and "Medications Development for Substance-Related Disorders," to be reviewed later in the year.

   Dr. Volkow summarized some research from the Intramural Research Program and the Center for the Clinical Trials Network. She noted that it was the 10th anniversary of NIDA's CTN and presented several CTN protocols in the development phase. Further, the CTN was active in the recent NIDA blending conference, "Evidence-Based Treatment and Prevention in Diverse Populations and Settings" which brought in over 1300 registrants to discuss a variety of promising treatments, with a special track on American Indian/Alaska Native research and treatment. The CTN role in helping in the harmonization for electronic medical records for patients with substance use disorders was noted. Also noted was the importance of considering clinical trials that combine medications rather than explore a single medication, as is typically the case. Thus, the CTN protocol using buprenorphine in combination with naltrexone for cocaine use reduction (CURB) is particularly important.

   The Division of Basic Neuroscience and Behavioral Research is supporting an RFA entitled "Deep Sequencing and Analysis of Pharmacogenomic Regions: Discovery and Analysis of Genetic Variants Contributing to Drug Abuse and Addiction." Applications in response to this RFA will be reviewed later in the year. The Division of Clinical Neuroscience and Behavioral Research issued an RFA on "Cognitive Remediation Approaches to Improve Drug Abuse Treatment Outcomes," and the Division of Epidemiology, Services & Prevention Research has been working closely with the AIDS Research Program. One outcome has been an RFA, joined by NIMH and NIAID, entitled "Seek, Test and Treat: Addressing HIV in the Criminal Justice System" that has led to a large number of applications. Dr. Volkow also noted that the XVIII International AIDS conference in July in Vienna, Austria, will provide an opportunity to discuss how evidence-based policies and programs can be expanded and will explore the influence of global drug policy on HIV prevention, treatment, care and support for people who use drugs. She noted the slowly growing recognition of the importance of including substance abusers in clinical trials for HIV treatments.

   Dr. Volkow then described the NIDA research track at the American Psychiatric Association annual meeting in New Orleans in May entitled "Neurobiological Circuits of Addiction: Significance for Psychiatric Practice" and noted other announcements in which NIDA is participating.

   Council thanked Dr. Volkow for her presentation. Council discussion included the consequences of big pharma withdrawing from work on psychiatric illnesses, the role of needle-sharing programs in reducing HIV transmission among injection drug users, ways NIDA can work with other Institutes on common problems in risky behaviors and HIV transmission, the consequences of stigma to the drug abuse field and ways to combat it, NIDA's role in providing science-based results that can be used by policy makers, and concerns about privacy issues for those who seek testing or treatment, given the stigma associated with both drug abuse and HIV. The potential of the Cures Acceleration Network (CAN) was also noted, as was the need for infrastructure development and partnerships between larger and smaller pharmaceutical companies for drug abuse medication development. The importance and challenge of harmonizing electronic medical records used by different organizations was noted, as was the importance of medical personnel sharing information so that, for example, dentists would know about their patients' drug use/abuse status. It was also noted that this was an opportune time to incorporate genetic studies into combination therapy trials to try to identify individuals who would be most likely to have issues related to medication toxicities and resist compliance. It was noted that consent to treatment for adolescent populations needs to be included in discussions of electronic health records and privacy issues. The need for harmonization of tools and measures in prevention and treatment was noted, as was the complexity of measuring the environment. Some of the challenges of harmonization across agencies were discussed, as was the recent 60 Minutes program and ways to educate the public. Also discussed was the role of FDA in regulating drug combinations, as well as the role NIDA might play in terms of knowledge synthesis for FDA and other agencies to ensure that the best scientific information on which to base new regulations and policy is available.

4. Report of NIDA's Science of Genetics Work Group - Eric Nestler, Ph.D., M.D., Chair, NIDA's Science of Genetics Work Group

   Dr. Nestler, as chair of the Science of Genetics Review Work Group, began his presentation by noting the assignment of the work group: to provide input to fortify NIDA's current human genetics research program through examining a range of emerging scientific opportunities and to recommend how best to maximize NIDA's substantial scientific investment in human genetics research. The work group met twice and communicated through email and telephone conversations. Information was obtained from NIDA staff and representatives of other Institutes. Dr. Nestler identified the members of the work group. He then addressed the state of the science, beginning with a brief overview of some epidemiological and population genetics findings and then addressing some issues in molecular genetics. He noted the complexity of gene finding, illustrating the genetic contributions to human disease through a chart showing allele frequency and effect size and reviewing briefly methodologies to identify addiction-related genes. These include candidate gene association studies, genome-wide association studies and next or second generation (deep) sequencing studies.

   Dr. Nestler then turned to the findings and recommendations of the work group, the first of which was the need to take a balanced approach. He noted that the available technologies are changing so rapidly that the work group could not specify which approach(s) would be most appropriate for NIDA. Rather, a balanced approach is needed, an approach that must be responsive to technological advances, i.e., more deep sequencing as it becomes less expensive. He also noted that balance is needed in other dimensions, e.g., cross sectional vs. longitudinal samples, though large samples would be needed in both cases.

   He noted that the current GWAS efforts are most advanced for nicotine and that it is important to balance with GWAS for other drugs of high priority and to incorporate GWAS technology into ongoing studies, i.e., using newer platforms that include low frequency, in addition to common, variants. The deep sequencing of selected genes includes genes robustly implicated in different phases of the addiction process in the most sophisticated animal models and epigenetic regulation of such candidate genes should be considered. The role for "deep phenotyping" was also considered, and the question was raised of whether more extensive phenotyping would assist in gene finding, as was the question of whether such deep phenotyping (behavioral, brain imaging, etc.) was consistent with the large scale genotyping needed. The work group concluded that deep phenotyping is essential to follow up on genetic hits.

   Ensuring the highest scientific rigor is essential, and Dr. Nestler noted that all human genetic studies supported by NIDA must adhere to the highest standards of research and that guidelines should be established to guide extramural scientists prior to submitting applications as well as to guide staff in funding applications. This is particularly an acute need for candidate gene studies involving some form of deep phenotyping, where sample sizes are usually small. Studies that are inherently under-powered should be avoided.

   Other recommendations included strengthening and empowering the NIDA Genetics Coordinating Committee (NGCC) and having that committee advise NIDA on funding applications which involve a human genetics component. Further, a database of the human genetics portfolio should be maintained to ensure that the strategic plan is being executed. NIDA might also consider recruiting additional extramural staff to ensure that all areas of expertise are covered. A number of other suggestions were made, including building bioinformatics, enhancing the human genetics program in the IRP, working increasingly with other Institutes and Centers, encouraging more data sharing among NIDA grantees as well as grantees of other ICs, ensuring rigorous scientific review of human genetics applications and emphasizing and executing the most effective translational work.

   Dr. Nestler summarized his presentation and pointed to needed future directions by noting that addiction genes exist and will be found, that NIDA must use the most advanced tools available to identify and characterize those genes, that improved oversight and top-down coordination would help ensure the most cost-effective and efficient research enterprise, that efforts are needed to make sure NIDA has the scientific infrastructure (both extramural and intramural) to take advantage of data and that it is not too soon to plan for how to advance discoveries into the clinic as rapidly and efficiently as possible.

   Council thanked Dr. Nestler for his report. There was then discussion about the utility of national repositories or data bases not only of biological samples but also of the raw sequencing data, about the complexity of identifying the proper phenotypes, including harmonizing phenotypes for the data that exists as well as developing better measures and having consistency of use across measures. The importance of longitudinal data was noted, but much of the extant data are cross sectional. Also noted was the need for infrastructures that allow collaboration and collection of longitudinal phenotypes of initiation, progression and cessation of drug abuse and addiction. There was also discussion about the relationship of GWAS and deep sequencing, with the strengths of each approach identified and the role of genetics driven deep phenotyping discussed. The opportunities to be found in focusing on normal human variability were noted. Finally, the possible continuing role for a work group to provide oversight and evaluation was discussed.

5. Public Comments

   There were no public comments.

6. Adjournment

   The 105th meeting of the National Advisory Council on Drug Abuse was adjourned at 1:30 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.