110th Meeting Minutes

February 14-15, 2012

The National Advisory Council on Drug Abuse convened its 110th meeting at 3:30 p.m. on February 14, 2012 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 February 14, 2012, was for the purpose of reviewing applications for Federal grant assistance and was open only to Council members and Federal employees. The open portion, which was open to the public on February 15, 2012, began at 8:30 a.m. The Council adjourned on February 15, 2012 at 12:25 p.m.

Council Members Present:
Nabila El-Bassel, D.S.W.
Elizabeth Howell, M.D.
Thomas Kirk, Ph.D.
Caryn Lerman, Ph.D.
Linda Mayes, M.D.
Eric Nestler, Ph.D., M.D.
Marina Picciotto, Ph.D.
James Sorensen, Ph.D.
Steven Wolinsky, M.D.
Jon-Kar Zubieta, Ph.D., M.D.

Council Chair:
Nora D. Volkow, M.D.

Executive Secretary:
Teresa Levitin, Ph.D.

Federal Employees Present:

Members of the Public Present:
Shelley Caplan - IQ Solutions, Inc.
Chris Carter, Ph.D., M.P.H. - Society for Women’s Health Research
Marguerite Clarkson, Ph.D. - PricewaterhouseCoopers
Yoshie Davison, M.S.W. - American Academy of Child andAdolescent Psychiatry (AACAP)
Susan Friedman - American Osteopathic Association
Nahla Hilmi - Contractor
Sharon Issurdatt, LCSW (MSW) - National Association of Social Workers
Alan Kraut, Ph.D. - Association for Psychological Science
George Lane, M.S. - Census
Julie Miller, Ph.D. - RTI International
Penny Mills, M.B.A. - American Society of Addiction Medicine (ASAM)
Alex Mottern, M.P.H. - IQ Solutions, Inc.
Geoff Mumford, Ph.D. - American Psychological Association
Andrew Neumann, M.A. - Synergy Enterprises
Vera Nordal, M.Ed. - IQ Solutions, Inc.
Lori Pellnitz, M.A. - SRA International, Inc.
Dan Tisch - BLH Technologies, Inc.
Genevieve Vullo - Contractor
Roy Walker - Synergy Enterprises, Inc.
Candace Webb, M.P.H. - Kelly Services, Inc.
Lori Whitten, Ph.D. - RTI International
Patrick Zickler - Synergy Enterprises, Inc.

Closed Portion of the Meeting - February 14, 2012

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. She reminded those present that the Federal Advisory Committee Act applies to Council meetings and that this portion of the meeting was closed to the public.

   Dr. 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 Clinical Neuroscience and Behavioral Research; 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; and the Office of Science Policy and Communications presented their applications for consideration by the Council. For each, Council provided concurrence with the initial scientific reviews en bloc. Council also approved the MERIT application and administrative supplements.

   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 - February 15, 2012

1. Call to Order

   Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order. She reminded the Council and audience that the meeting was open to the public in compliance with the Government in the Sunshine Act and indicated that time would be provided for public comment. Dr. Volkow called attention to future Council meetings: May 10, 2012 and September 6, 2012.

2. Consideration of the Minutes of Council

   The Minutes of the September 2011 meeting were approved as written.

3. Operational Procedures and Delegation of Authority - Teresa Levitin, Ph.D., Director, Office of Extramural Affairs, NIDA and Executive Secretary, National Advisory Council on Drug Abuse

   Dr. Levitin noted the NIH policy that that each institute and its advisory council develop a document outlining the operating procedures and delegation of authority relevant for grant review responsibilities of that council and institute staff. This document needs to be approved on a yearly basis, and NIDA Council traditionally reviews the document at its February meeting. This document is also made available to the Office of Extramural Research of the NIH for its review to ensure compliance with relevant NIH policy.

   Dr. Levitin noted that the document approved in 2011 had been sent to Council prior to the meeting, along with a request for feedback. No suggestions were received. Dr. Levitin then reviewed the document with Council to see if there might be any recommendations now. She highlighted each of the sections of the document, for example, the use of en bloc concurrence, approval of administrative supplements, and other matters. She explained which matters require Council action and which are the responsibility of NIDA staff, and she also assured Council members that any unusual matters, even if delegated to staff for action, would be brought to Council for their information.

   Council unanimously voted to approve the document.

4. NIDA Director’s Report - Nora D. Volkow, M.D., Director, NIDA

   Dr. Volkow began her report by announcing that Mary Affeldt had left her position as Associate Director for Management/Executive Officer and introducing her replacement, Glenda Conroy. She also announced that Dr. Markus Heilig had been selected as the Clinical Director for the joint NIDA/NIAAA IRP. Turning to the budget, Dr. Volkow pointed out that the NIDA budget for 2012 provided a 0.3% increase over the prior year and that the 2013 President’s Budget would provide a 0.2% increase, bringing NIDA to a total budget of $1,054,001,000.

   Dr. Volkow then turned to the recommendations to NIH from the Scientific Management Review Board (SMRB). On November 16, 2010, the recommendation was made to create a new institute focusing on substance use, abuse, and addiction research and related public health initiatives, to integrate the relevant research portfolios from NIDA, NIAAA and other institutes and centers, and to dissolve NIDA and NIAAA and move those portions of the portfolio not related to substance use, abuse, and addiction research to other, relevant ICs. Dr. Volkow described what is being done to develop a scientific strategic plan to implement these recommendations. The plan is to identify new scientific opportunities and public health needs that are not sufficiently addressed by NIH at this time, assess the suggested new scientific opportunities and public health needs, taking into consideration the current scientific strategic plans and missions of NIDA, NIAAA, NCI and other potentially affected ICs and develop a draft scientific strategic plan. Input has been – and will continue to be—solicited from staff, external stakeholders, and the public. Dr. Volkow presented the timeline, noting that the new institute is scheduled to stand up in October 2013 (FY 2014) and that before that time there will be solicitation for public stakeholder input through a Request for Information and public meetings. She encouraged Council members to provide their comments.

   Dr. Volkow listed the priority areas of NIDA: prevention research, treatment interventions, and medical consequences. She then presented data from the Monitoring the Future study on 12th grade high school students’ use of cigarettes and marijuana over the past month and the prevalence of their past year drug use. Marijuana use has increased; cigarette use is down in this sample. She noted the different types of drugs that are being used by high school students, including the increased use of stimulant medications. She then described a pathway of drug involvement with nicotine as a gateway drug, citing the research of Drs. Eric and Denise Kandell. Dr. Volkow then turned to the relatively new area of large data sets. The challenges for the analysis and interpretation of big data sets and issues of quality control and maintenance were described; the need for interdisciplinary teams, training, infrastructure and culture change was noted, as was the critical importance of open access to data. Big data sets are essential for the analysis of complex systems in genetics and epigenetics, proteomics, brain imaging and other areas of science, and the challenges of handling such data sets are formidable. Dr. Volkow then described the Big Data Advisory Committee to the Director of NIH. The Data and Informatics Working Group (DIWG) chaired by Drs. Tabak and DeMets has several subgroups to provide information to the DIWG on policies and investments needed to facilitate data sharing and integration, and the DIWG will develop recommendations to present to the ACD and the NIH Director on policies regarding the management, integration and analysis of research data and administrative data.

   Dr. Volkow then described plans to move brain imaging forward. These include the NIH Blueprint sponsoring a 2012 workshop on neuro-image data sharing issues, funding explicitly open-access projects, including the human connectome project and the Alzheimer’s disease neuroimaging initiative as well as supporting infrastructures/tools for sharing. Harmonizing instruments for clinical research will also move the field forward, and NIDA is announcing a major data-harmonization effort to do so. That is, NIDA is dedicated to advancing science by improving the yield of its research portfolio. One way to accomplish this is to provide investigators with a common set of tools and resources, and, toward this end, NIDA, in conjunction with NIAAA, NCI, NHGRI, OBSSR and the broader scientific community, have identified a series of core and specialty measures to promote the collection of comparable data across studies. Dr. Volkow then described the substance abuse and addiction core and specialty areas that researchers would be encouraged to include in every study or to include according to the focus of the study. She encouraged Council to provided feedback on these measures. She also presented new PAs and RFAs in the area of prevention intervention research and services research.

   In the priority area of treatment interventions, Dr. Volkow talked about the interest in D3 receptors and work in animal models, and she then presented data on meth users and higher binding of the Dopamine D3 receptor-preferring ligand as well as a study on buspirone showing that buspirone reduces cocaine self-administration in Rhesus monkeys. Other studies were also noted including a new CTN randomized controlled evaluation of buspirone for relapse prevention in adults with cocaine dependence. Dr. Volkow announced the latest recipients of the NIDA Avant-Garde medications development awards, Dr. Thomas Kosten, who will explore a human methamphetamine vaccine and Dr. Peter Burkhard for a peptide nanoparticle nicotine vaccine.

   In the priority area of medical consequences/HIV and drugs, several studies were noted. The cumulative estimated numbers of AIDS diagnoses among adults and adolescents, by transmission category, was presented, as were data on antiretroviral adherence, the role of methadone maintenance therapy, and other findings. Dr. Volkow pointed to the importance of considering the contribution of injection drug use to actual cases of HIV. Dr. Volkow briefly described the Population Assessment of Tobacco and Health (PATH) study and the follow-up to the NACDA document on points to consider regarding tobacco industry funding of NIDA applicants. She noted that NIDA received a number of letters in support of this tobacco industry funding statement of points to consider.

   Other NIDA activities include the new NIDA website and the revision or publication of several NIDA publications, including the revision of booklet on the principles of drug abuse treatment for criminal justice populations. The second Annual National Drugs Facts Week was very successful. The winning submissions for the 2011 Teen Substance Abuse Awareness Through Music Contest were presented. The NIDA research tract at the American Psychiatric Association meeting was briefly described.

   Council thanked Dr. Volkow for her presentation. Many issues were raised including the use of “addiction” in the DSM-5, the importance of investing in bioinformatics and open access to data, gateway models for other behaviors such as obesity, the new institute and ways Council might assist in its development, views of the streamlined Director’s Report to Council document, whether the NIAAA and NIDA Councils should try to meet again and, if so, before or after the strategic plan is presented, collaboration with NSF, challenges and costs of storage and maintenance of large data sets, and bringing more people trained in mathematics and physics into biological fields.

5. Promoting Sharing of NIH-Funded Brain Imaging Data: Promises and Challenges - Steven Grant, Ph.D., Branch Chief, and James Bjork, Ph.D., Program Official, Clinical Neuroscience Branch, Division of Clinical Neuroscience and Behavioral Research (DCNBR)

   Dr. Grant began his presentation by listing the members of the Neuroscience Blueprint Workgroup on Neuroimaging Data sharing, noting that 12 ICs and 19 representatives are participants. There have been nine workgroup meetings since April 2011, and accomplishments have included assessment of existing IC imaging data sharing activities; assessment of existing imaging data repositories, an RFI that elicited much expert commentary, focus group activity to obtain information from R01 “end-user” grantees and journal editors, and a proposal for a workshop. Dr. Grant then described the workgroup’s preliminary assessment of extant sharing policies in different ICs, noting that there is no formal IC-wide imaging sharing policy in place in any IC, though there are a few disease-state specific or protocol/repository exceptions. He then described a preliminary assessment of existing human image repositories or networks at various ICs as well as some extramural/grass roots ones.

   Dr. Grant then turned to some of the responses to the RFI notice. Respondents were primarily NIH funded, and there were many high quality responses from key sharing players, though they were more typical of people involved in large projects or centers than of the typical R01 awardee. More than one respondent noted that to be truly useable, a centralized database might be required; an expanded mandate to share image data might be satisfactory if certain conditions were met; resting-state fMRI is the lowest-hanging fruit but task fMRI is also desirable, albeit complicated; journals must establish ways to handle increasing amounts of secondary papers, including issues of credit; and NIH or other leading institutions should provide consent/IRB boilerplate language and guidance. It was also noted that there are several maturing infrastructures already in place, that there is significant pushback against enforced standardization of image collection parameters/methods and that there is significant endorsement of standardization of meta-analysis elements and image collection parameters/activation foci/task event timing that are furnished in tandem with image data. Further, there is endorsement of limited/partial standardization of phenotypic measures and concern over third party use of shared data. There is a need to establish a mechanism for institutional/NIH recognition and tracking of use of one’s data by others.

   Dr. Grant then described the “end-user” focus group of approximately 18 typical R01-type extramural investigators, graduate students, representatives from INCF, NITRC, BIRN and others. Dr. Grant stated that the question of whether investigators like the idea of expanded sharing can be answered with a qualified “yes”. Such sharing allows investigators greater statistical power, options for exploratory analysis and the development of new analytic methods and it also allows new investigators to obtain pilot data. It also expands training opportunities, a critical factor not only for neuroscientists at places that do not have the capacity to collect data but also for undergraduates. Dr. Grant also identified issues that need to be considered; these include implementation issues such as data model/scope, harmonization/standardization, intellectual property as well as funding and resources. Dr. Grant presented a conceptual framework of data sharing models with different data scopes and costs. He closed his remarks by suggesting some next steps and workshop ideas guided by the “straw man” principle that “NIH commits to providing open-access to brain imaging data” and covering infrastructures, human subject issues, intellectual property issues and data sharing guidance/common data elements.

   Dr. Bjork then described the HCP data collection, processing and sharing processes. He noted that this data sharing architecture means that there will be on-the-fly connectivity analyses of HCP datasets of interest such that scientists will select samples of interest based on search criteria and will be able to dynamically compute average connectivity maps for that cohort and visualize and compare connectivity maps. He illustrated some of the questions that might be addressed. Dr. Bjork concluded by noting that although expensive, this approach would yield tremendous new information and that investment in this sort of infrastructure and sharing would greatly advance the field.

   Council thanked Drs. Grant and Bjork, noting the timeliness and importance of the issues raised. Discussion included recognition of the substantial amount of data that would be gathered, the challenges of managing and transferring data sets of this size, and the importance of standardization and harmonization. Issues of publication, citation and embargo were also discussed, and it was noted that many people and organizations are looking at these issues.

6. Update on Collaborations with the FDA - Wilson Compton, M.D., M.P.E., Director, Division of Epidemiology, Services and Prevention Research (DESPR)

   Dr. Wilson Compton began his presentation by introducing the concept of regulatory science. He then noted that tobacco use is the leading preventable cause of disease and death in the United States. He pointed out that there are more deaths from cigarette use and second hand smoke than from HIV, illegal drug use, alcohol use, motor vehicle injuries, suicides and murders combined. Dr. Compton then presented data on changes over the last 110 years in adult per capita cigarette consumption in the USA, noting, for example, an important transition in the 1950s with the publication of the first conclusive evidence that tobacco was a cause of lung cancer followed by the Surgeon General's Report in 1964 and many policy changes since that time. He also presented data from the Monitoring the Future Study on cigarette use among students in the 8th, 10th, and 12th grades, noting that tobacco use is at its low point in the history of this survey for all three grades.

   Dr. Compton then described the Family Smoking Prevention and Tobacco Control Act (FSPTCA) enacted in 2009 that gave the FDA the authority to regulate tobacco-product advertising, labeling, marketing, constituents, ingredients and additives. These regulatory changes are expected to influence tobacco-product risk perceptions, exposures, and use patterns in the short term, and to reduce tobacco-related morbidity and mortality in the long term. Dr. Compton described what the Act authorizes the FDA to do (e.g., regulate the manufacture and marketing of tobacco products, to require disclosure of tobacco product ingredients, and to conduct research in support of tobacco product regulation), as well as the limitations of that Act (e.g., FDA does not have the authority to set nicotine levels to zero, to require prescriptions for tobacco products, or to regulate clean indoor air policies). The FDA tobacco control goals include preventing youth tobacco use, helping those who use tobacco to quit, promoting public understanding of contents and consequences of use of tobacco products, and developing a science base that will support meaningful product regulation to reduce the toll of tobacco-related disease, disability and death. Dr. Compton then listed key FDA tobacco control accomplishments to date. Examples of specific actions include banning flavored cigarettes, restricting access and marketing of cigarettes and smokeless tobacco products to youth, and requiring graphic cigarette health warnings on cigarette packages and advertisements. Other key accomplishments include starting the Center for Tobacco Products (CTP) and engaging in the development of a robust research program. He briefly described the mission and resources of the CTP.

   Dr. Compton posed the question of how the FDA could accomplish its extensive research goals and answered that question by asserting that collaborations, especially with NIH, are the key. He described the NIH-FDA tobacco regulatory science workgroup composed of representatives from 16 ICs and the Office of the Director. He listed some of the accomplishments of this workgroup, including studies supported and in process. Dr. Compton then described studies funded by FDA and administered by NIDA, most notably the Population Assessment of Tobacco and Health (PATH) Study which incorporates a model of tobacco use that takes into account host, agent, vector and environment domains as well as interactions among all these factors. He noted that results from the PATH study will inform the impact of FDA regulatory authority over tobacco products and help to inform future activities. Specific aims of this large-scale, longitudinal cohort study of the general U.S. population ages 12 and older include identifying trends in tobacco use, including new products; monitoring change in risk perceptions and other attitudes; collecting biomarkers of tobacco use and disease processes, and assessing critical subgroups. The currently planned study sample and critical subgroups, domains of outcomes and mediators/moderators were described, and a study timeline was presented.

   Dr. Compton then described other relevant projects and activities, including a FDA funded and NIDA administered P50 Center evaluating the potential impact of reduced nicotine levels in cigarettes. He then summarized NIDA’s involvement in NIH/FDA tobacco control collaborations and closed by describing the next steps for the near future and the overall vision for NIDA/FDA collaboration. That vision is to support science to gather data that will monitor, inform, support and enhance tobacco control efforts.

   Council thanked Dr. Compton for an excellent presentation. Council discussion included questions about studying gender differences, applications submitted to NIDA that might be supported by the FDA, a relevant IOM report on research designs, nicotine use and schizophrenia, budget and funding matters, an upcoming FDA meeting to discuss research priorities around tobacco products, and possible contributions from basic science/neuroscience.

7. Operating Procedures and Delegation of Authority - Teresa Levitin, Ph.D., Office of Extramural Affairs, and Executive Secretary, NACDA
8. Presentation of Concept Clearances

   Three concept clearances were presented. First, Dr. Aidan Hampson presented a concept on improved bioassays to support outpatient clinical trials. He raised two crucial issues: the need to develop improved markers to assess whether subjects take the medication (compliance markers) and the need to develop bioassays that would determine the frequency of daily illicit substance use and track the dose used. The advantages of urinalysis were noted, as was its major Achilles heel- the limited number of assessments (data points), which makes accurate real-world assessment of drug use difficult at best. It was noted that compliance markers to identify adherence are key to successful clinical trials, in that poor adherence makes a failed trial look like a failed medication. The need for development of two categories of new compliance markers were discussed: qualitative assays rapid enough to be conducted in the clinic and quantitative assays that may take longer, but can provide an accurate assessment of the dose and frequency of drug use throughout the trial. Dr. Hampson summarized his presentation by noting that the proposed FOA would seek improved compliance markers that are safe, pharmacologically inactive and (probably) eliminated in urine. The FOA will also seek development of new bioassays/systems that are affordable, verifiable, minimally invasive and easy to use at home. In this way sufficient samples might be gathered to accurately track both the dose and frequency of drug use throughout the trial. Council raised a number of issues and enthusiastically supported this initiative.

   Second, Dr. Phil Skolnick presented an initiative to test the hypothesis that reductions in drug use (as opposed to abstinence) are associated with beneficial health outcomes. The proposed initiative would support both prospective and retrospective research to assess health outcomes associated with reductions in drug use. This research might include, but would not be not limited to, identification and/or validation of strategies/methods/tools (including biomarkers) that could monitor well-characterized health outcome(s)/effect(s) associated with reductions in the use of a specific drug. This FOA would underscore NIDA’s recognition of the need to identify health outcomes associated with reductions in drug abuse. This initiative is extremely important for the future approval of medications to treat substance use disorders. It was deemed so important that Dr. Skolnick, rather than the program officer, presented it to Council. Council agreed with the importance of this approach and noted the substantial challenge in persuading regulators that reduced drug use may have salutary health outcomes.

   Third, Dr. Jacques Normand presented a new initiative to complement the AIDS Avant-Garde program. While the Avant-Garde award focuses on high-risk, high-payoff research and does not require a detailed research plan, this new program while also focusing on innovation, would require a more detailed research plan and more preliminary data. It is designed to attract exceptionally talented investigators with a track record of conducting groundbreaking, exceptionally innovative original and/or unconventional research focused on HIV/AIDS and drug abuse. This initiative is intended to provide support for collaborative investigative teams or individual scientists to conduct projects, which, if successful, would have a major impact on HIV/AIDS and drug abuse. Projects may be in any area of research within NIDA’s portfolio. Council had no questions on this initiative.

9. There were no Public Comments
10. Adjourn

    The 110th meeting of the National Advisory Council on Drug Abuse was adjourned at 12:25 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.