May 11, 2011
The National Advisory Council on Drug Abuse convened its 108th meeting at 8:30 a.m. on May 11, 2011 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 11, 2011, 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, on May 11, 2011, was from 10:30 a.m. until 2:30 p.m. The Council adjourned on May 11, 2011 at 2:30 p.m.
Council Members Present:
Francisco Castellanos, M.D.
Steven Childers, Ph.D.
Thomas Crowley, M.D.
Nabila El-Bassel, D.S.W.
Anita Everett, M.D.
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.
Hazel Szeto, Ph.D., M.D.
Steven Wolinsky, M.D.
Jon-Kar Zubieta, Ph.D., M.D.
Council Members Absent:
R. Dale Walker, M.D.
Ex Officio: John P. Allen, Ph.D., M.P.A.
Nora D. Volkow, M.D.
Teresa Levitin, Ph.D.
Approximately 157 federal employees were present, and 10 additional observers attended the open session, including representatives from constituency groups, liaison organizations, and members of the general public.
Closed Portion of the Meeting - May 11, 2011
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.
In turn, the Director or a designee for 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; and the Division of Epidemiology, Services and Prevention Research presented their applications for consideration by the Council. For each, Council provided concurrence with the initial scientific reviews en bloc. Council also approved all MERIT applications.
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 11, 2011
Call to Order
Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order, and introduced and welcomed the new Council members: Drs. Nabila El-Bassel, Elizabeth Howell, Thomas Kirk, Linda Mayes and Marina Picciotto. 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 12-13, 2011; February 14-15, 2012, May 8-9, 2012, September 5-6, 2012.
Consideration of the Minutes of Council
The Minutes of the February 2011 meeting were approved as written.
NIDA Director's Report - Nora D. Volkow, M.D., Director, NIDA
Dr. Volkow began her Director's report by presenting a budget update. She noted that in both 2009 and 2010 there had been a 2.6% increase over the prior year. In 2011, the President's Budget called for a 3.3% increase but the 2011 full year continuing resolution (CR) was a 0.9% decrease, giving NIDA a total budget of $ 1,050,542 (in thousands). Dr. Volkow then provided a pie chart indicating how the actual FY 2010 portfolio was distributed, noting that 46% of the budget was devoted to basic and clinical neuroscience and behavioral research; 23%, to epidemiology, services and prevention research; 12%, to pharmacotherapies and medical consequences research; 4%, to the clinical trials network; 8%, to intramural research and 6%, to RM&S. She reiterated NIDA's commitment to funding basic clinical and neurosciences research.
In reporting on what was new at NIH, Dr. Volkow provided information about the proposed National Center for Advancing Translational Sciences (NCATS). She listed meetings that have been held to describe the proposed Center to relevant stakeholders and indicated what functions and activities would be incorporated into this new Center. She also described the H3Africa initiative, a new program to facilitate a contemporary research approach to the study of genomics and environmental determinants of common diseases with the goal of improving the health of African populations. To accomplish this, the H3Africa Initiative aims to create and support the development of necessary expertise among African scientists and to establish networks of African investigators. NIDA is very interested in participating in this new initiative.
Dr. Volkow then turned to recent NIDA activities and events, noting that ARRA funds had been successfully used to support many short-term projects. She reminded Council of the Institute's priority areas: prevention, treatment and medical consequences. Dr. Volkow reported on findings from Brody et al. on the effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain. New PAs and RFAs relevant to the broad priority area of prevention were presented. In the treatment arena, interesting research findings on the design, preparation, and characterization of high activity mutants of human butyrylcholinesterase specific for detoxification of cocaine (Xue et al.) were presented. Several new PAs and RFAs relevant to treatment were also presented. These RFAs include the Translational Avant-Garde Award Program for Medications Development for Diseases of Addiction, a Medication Initiative for Tobacco Dependence (MITD): A New Product Development Partnership, and a Grand Opportunity in Medications Development for Substance-Related Disorders. In the HIV and Drugs area, Dr. Volkow presented several important studies as well as new PAs and RFAs, including an RFA entitled "Seek, Test, Treat, and Retain: Addressing HIV among Vulnerable Populations" and the Avant-Garde Award Program for HIV/AIDS Research.
Other activities have included development of a proposed organization for NIH Pain Consortium Centers of Excellence, with seven participating Institutes/Centers (as of May 2011) and NIDA serving as the contracting IC. Dr. Volkow discussed the serious problem of the abuse of psychotherapeutics, with the abuse of opioid medications as the most significant of these problems. She pointed to the increasing number of opioid overdose deaths and increased treatment admissions for opioid abuse and reiterated the importance of studying pain and its treatment and noted the limited training of medical students about pain. The Surgeon General's Expert Panel on Prescription Drug Abuse in Youth met in March of 2011, and in April National Prescription Take Back Day took place. This was an opportunity to turn in unused or expired medication for safe disposal.
Dr. Volkow also described the NIH Blueprint for Neuroscience Research Workgroup on Open Access for Neuroimaging Data. This workgroup has met twice thus far, and there are 18 representatives from 10 ICs working on this important project. The group has tallied existing policies or infrastructures, noting that there is no formal IC-wide brain imaging sharing policy in place in any IC but specific projects/awards have data sharing elements. A variety of other topics are being discussed by this workgroup, which is chaired by Dr. Steve Grant at NIDA. NIDA has organized a research tract for the American Psychiatric Association annual meeting; several symposia are planned with the common theme of advancing psychiatric practice through the science of addiction.
Also of relevance: The Addiction Performance Project (a NIDAMED CME program) will feature three 2011 performances of a dramatic reading of Act III of O'Neill's Long Day's Journey into Night. For the INTEL International Science and Engineering Fair, NIDA will again sponsor addiction science awards for relevant projects. There are 10 RFAs from other ICs that NIDA has joined; preliminary planning for the next wave of common fund initiatives is taking place and a Congressional briefing sponsored by the Friends of NIDA in conjunction with the Addiction, Treatment and Recovery Caucus was an opportunity to present information about marijuana use disorders, dependence and treatment research.
Council thanked Dr. Volkow for her presentation and noted a number of issues: the limitations in provider education and understanding of how to use genetic information; the implementation of the recommendations of the genetics workgroup; the newer formulations of opioids that may be more abuse-resistant and the need for incentives to develop them and insurance companies to accept them; the new timeline for the creation of the new institute on substance abuse disorders; and the success of the Avant-Garde programs.
Update on the Intramural Program - Antonello Bonci, M.D., Scientific Director, Intramural Research Program (IRP)
Dr. Bonci presented his vision of the intramural program, and that vision is to create a cutting edge, translational, flexible, collaborative, open, transparent environment, a program that should provide scientific freedom, and is inspired by the Howard Hughes Institute. To achieve this vision, he has moved in a number of new directions, many of which he described. Specifically, after presenting the BSC membership, he noted that the BSC has been changed in several ways: a smaller Board with fewer ad hoc members, one rather than two meetings a year, electronic scoring with a greater emphasis not only on the potential impact of scientific projects but also on the high risk and impact on a whole field of research.
Further, he has instituted a NIDA IRP medications discovery program. This program will be more focused, and Dr. Bonci explained the importance of prioritizing potential targets and the selection of (+)-naloxone for study. Several IRP staff are involved in this work, with plans for the PK and toxicology assessment to be done through DPMCDA. He noted the enthusiasm of IRP staff for this project and the close working relationship between Drs. Amy Newman of the IRP and Phil Skolnick of DPMCDA.
The clinical program that was in place when Dr. Bonci arrived was presented, and it was noted that the various components were not optimally integrated. In contrast, the new clinical program configuration that is being implemented will better develop and prioritize projects as well as allocate resources. Dr. Bonci noted that the creation of a Board of Directors is being considered. This could be comprised of the Clinical Director, Clinical Section Chief and the Scientific Director who will have responsibility for this new integrated clinical problem.
Several functional interactions with NIAAA were described. Some collaborative studies with NIAAA were mentioned. Dr. Bonci noted that his vision is that of a unified clinical program with NIAAA and that he and Dr. Markus Heilig and others are moving in that direction. Dr. Bonci briefly described the joint efforts of Drs. Brandon Harvey and Bruce Hope and their optogenetic and transgenic core facility, the first of its kind in the NIH intramural programs. The tools they are developing will be widely used. The role of the Diversity and Outreach Committee was also described and its members were listed. Two activities were highlighted: 1) the NIDA Scientific Director's Fellowship for Diversity in Research and 2) the Partnership with the Science Club at Patterson High School. Dr. Jean Lud Cadet is the Associate Director for Diversity and Outreach and is actively pursuing diversity goals with the active support of Dr. Bonci and others.
Several other new initiatives were presented. These include creation of a space committee; creation of journal club/data presentation weekly meetings; the expansion of roles to include a Women Science Advisor and a Tenure and Promotion Committee which will implement quadrennial review of staff scientists/staff clinicians; the collection of information on capital equipment that can be shared; and the collection of information on behavioral models currently present at the IRP.
Some core facilities were described, and additional information on new initiatives was provided. These include a scientific retreat, recruitment of a cognitive neuroscientist, and joint recruitment with NIAAA of a clinician. Initiatives with Johns Hopkins were identified, and Dr. Bonci pointed to the many opportunities there are to be found in working with Hopkins, something that has not previously been systematically explored. Several organizational changes were also presented, including naming Dr. Amy Newman as the Deputy Scientific Director.
Council thanked Dr. Bonci for his presentation, asked about the program for developing women scientists and praised Dr. Bonci for how quickly and competently he was implementing needed changes in the Intramural Research Program.
Developing Medications to Treat SUDs - Phil Skolnick, D.Sc., Ph.D., Director, Division of Pharmacotherapies and Medical Consequences of Drug Abuse, (DPMCDA)
Dr. Skolnick began his presentation with a brief history of the Division of Pharmacotherapies and Medical Consequences of Drug Abuse, noting that the Division was created by Congressional mandate over 20 years ago to establish a program to develop biological and pharmacological approaches to treat heroin/cocaine addiction. Over the years, that initial charge has expanded to include developing medications to treat nicotine, cannabis, methamphetamine, and prescription opioid dependence.
In January of 2011, a scientific advisory workgroup was convened to evaluate how the Division was using its resources to meet its charge and to find ways to more effectively align current practices with contemporary views of drug discovery and development. Dr. Skolnick identified the workgroup members, noting that they were drawn largely from industry and all had neuroscience backgrounds. The primary recommendation of the workgroup was to focus and trim the program so that every compound in development would have a target product profile, by which they meant every compound in development should have a trajectory for either registration or partnering. In the workgroup's view the current portfolio of potential targets and therapeutic strategies is unsustainable, given the Division's budget.
Dr. Skolnick expressed his view that the Division program was something of a hybrid, with hypothesis testing that is opportunistic and based on compound availability, and that, because the Division is not a pharma, it is necessary to be opportunistic, basing work on compound availability and selecting drugs or targets with activity in multiple models against multiple drugs of addiction.
Also of interest are drugs in later stage (Phase II) development that have either failed in other indications or were parked for funding or programmatic issues. Such molecules are of interest because they have already been found to be safe and fairly well tolerated. Also, largely because of contraction of programs in psychiatry discovery, more small molecules may become available for clinical trials. Registration (labeling change for a generic) enables reimbursement by third party payers and de-risks use of a compound for prescribers.
Dr. Skolnick pointed out that his Division differed from other Divisions at NIDA because the primary deliverable is a product or advancement of a compound in a clinical trial, not a paper for publication. This requires a different way of thinking about science, and he noted the need to educate extramural scientists as to the expectations of this Division for products.
The workgroup also recommended that the Division do more to align its grant and contract programs to conduct both preclinical and clinical studies in a more efficient manner. Dr. Skolnick acknowledged the realities of supporting investigator initiated studies but, at the same time, pointed out that the traditional R01/5 year mechanism is not the most appropriate vehicle for medications development. Rather, the contract mechanism allows for greater flexibility and control of resources. Dr. Skolnick showed a graph of Division funding of medications development using grants and contracts mechanisms and noted that the workgroup recommended, to the extent feasible, that there be an increase in contract funding and a decrease in the relative amount of Division resources in grant programs. Because of grant duration, this recommendation can only be implemented gradually. Also, as more compounds become available for clinical testing from industrial sponsors, this may be the only acceptable method for hypothesis testing.
Dr. Skolnick raised the question of whether medications development is compatible with funding through grants. He then noted that ARRA successes provide a paradigm for funding medications through grants and that medications development grants should be larger, with shorter timeframes and clearly defined milestones. Review committees need scientists familiar with the drug development process to ensure appropriate review. Dr. Skolnick then described new funding opportunities for 2011-2012; these include the Translational Avant-Garde Award, and the Grand Opportunities for Medications Development program.
A third workgroup recommendation was that the Division should focus on preparing to market its medications to a commercial partner (a pharma or biotech company) capable of sustaining development through late-stage clinical trials and commercialization. Specifically, this implies focusing on providing proof of concept/pharmacological mechanism and presenting this evidence to companies in their language. The Division's "sweet spot" should be the de-risking molecules through proof of concept. Because pharma has not embraced the development of medications to treat SUDs, the Division's approach must be opportunistic, with the opportunity to advance compounds/mechanisms throughout the development cycle. Several examples based on compound availability were suggested.
The workgroup also recommended using available mechanisms such as center grants to build up an infrastructure for conducting the pharmacokinetic and pharmacodynamic studies needed to establish proof of concept and proof of mechanism. Another recommendation was using centers of excellence to conduct relevant work. Pharma sponsors are often unwilling to provide compounds in development to grantees, and Dr. Skolnick stated that the Division is currently monitoring its P50 centers to ensure that they are capable of conducting GCP studies and clearly communicating that the number of trials completed/subjects enrolled, not the number of publications, is the criterion of excellence. Dr. Skolnick then asserted that every trial should measure compliance and he presented data from a study that had not had adequate compliance and failed after spending millions of dollars.
He concluded by identifying several challenges, including uncertainty in funding levels and the need to leverage resources (as well as ways to do so), the need to find new sites (including foreign sites), and the changing NIH landscape, and then he reiterated the recommendations of the working group that, if implemented, could lead to more successful and rapid medications development.
Council thanked Dr. Skolnick for his presentation, agreed with the importance of focusing and trimming the portfolio and asked how such decisions would be made. Ways for extramural scientists to work with pharma were also discussed and the complications and complexities of doing so were acknowledged.
NIDA's AIDS Research Program Update - Jacques Normand, Ph.D., Director, AIDS Research Program
Dr. Normand noted that his presentation would cover three areas: 1) an overview of NIDA's Avant-Garde Program; 2) an overview of other NIDA AIDS Research Program recent initiatives; and 3) an overview of other NIDA AIDS Research Program recent activities.
The Avant-Garde program began in 2008 with three awards. In 2009 there were four awards and there was one award in 2010. For 2011 there are five applicants who will be interviewed in the summer, and in 2012 the program will, for the first time, be open to foreign applicants. Dr. Normand reminded Council about the purpose of the program, described how it is publicized as well as how the applications are evaluated and scored at both the initial and interview stages. Also he presented information about each of the eight awardees. He noted that on April 18 the awardees met for the purpose of fostering communications between Avant-Garde awardees and clinical researchers to accelerate translation of basic science findings into clinical studies. In this successful meeting between drug abuse HIV researchers and Avant-Garde awardees the need for access to clinical samples from well-characterized subjects was identified, as was the need for basic and clinical researchers to work more closely together to develop protocols for collection, preparation, storage and cataloging of samples and also to address privacy and consent issues.
Recent initiatives have included the Seek, Test, Treat and Retain program supported by a number of agencies. Dr. Normand noted the work of Dr. Julio Montaner, a 2008 Avant-Garde awardee, on HIV treatment as prevention in drug-using populations. A number of RFAs have also brought in new and important research, including 12 awards in criminal justice. Dr. Normand pointed to a recent publication in Russian of interest and to an international workshop on treatment as prevention that was held in May, and he emphasized the importance of prevention.
Turning to the topic of a cure, Dr. Normand noted that three Avant-Garde Principal Investigators are doing relevant research on latent virus and that a recent RFA, Epigenomics and Non-Coding RNAs in HIV/AIDS, led to seven awards. Another RFA, Systems Biology, HIV/AIDS, and Substance Abuse led to five awards.
Dr. Normand mentioned the national strategic plan from the White House, noting that there are three primary goals: reducing new HIV infections; increasing access to care and optimizing health outcomes for people living with HIV; and reducing HIV-related health disparities. Dr. Normand then presented more specific information about NIDA efforts in each of these areas, noting how NIDA programs are aligned with this strategic plan. He also presented three CCTN HIV/AIDS trials, identified recent international activities, including an international publication, and noted some important career development initiatives. These initiatives include the AIDS-Science Track Award for Research Translation, an R03 program that has yielded 28 awards since 2008.
Council thanked Dr. Normand for his presentation and commended NIDA for leading the way in identifying important issues and supporting important research in this area.
Mr. Andrew Kessler, representing a new organization called ADAPTE International, described this organization, noting that it provides advocates with innovative, reasonable, effective and proven strategies to prevent and treat substance abuse while focusing on the restoration and welfare of individuals, families and communities. He also noted that, supported by evidence-based strategies and sound policies, ADAPTE International will bring together prevention, enforcement, treatment, recovery and community based groups and coalitions, working in partnership with government to identify, address and resolve substance abuse issues.
The 108th meeting of the National Advisory Council on Drug Abuse was adjourned at 2:30 p.m.
I hereby certify that the foregoing minutes are accurate and complete.
Nora D. Volkow, M.D.
National Advisory Council on Drug Abuse
Teresa Levitin, Ph.D.
National Advisory Council on Drug Abuse
Note: Informational materials provided to the public at the open session of the meeting may be obtained from the Executive Secretary.