112th Meeting Minutes

September 5-6, 2012

The National Advisory Council on Drug Abuse convened its 112th meeting at 2:00 p.m. on September 5, 2012 in Conference Room C, 6001 Executive Boulevard, Bethesda, Maryland. Dr. Nora Volkow, Director, NIDA, opened the meeting. The closed portion of the meeting on September 5, 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 September 6, 2012, began at 8:30 a.m. The Council adjourned on September 6, 2012 at 12:35 p.m.

Council Members Present
Nabila El-Bassel, D.S.W.
Carl Hart, Ph.D.
Elizabeth Howell, M.D.
Terry Jernigan, Ph.D.
Thomas Kirk, Ph.D.
Robert Lenox, M.D.
Caryn Lerman, Ph.D.
Barbara Mason, Ph.D.
Kelvin Lim, M.D.
Linda Mayes, M.D.
Michael Nader, Ph.D.
Eric Nestler, Ph.D., M.D.
Marina Picciotto, Ph.D.
John Rotrosen, M.D.
James Sorensen, Ph.D.
Roger Dale Walker, M.D.
Steven Wolinsky, M.D.
Jon-Kar Zubieta, M.D.

Council Chairs
Nora D. Volkow, M.D.

Executive Secretary
Teresa Levitin, Ph.D.

Federal Employees Present:

Members of the Public Present
Yoshie Davison, M.S.W. - American Academy of Child and Adolescent Psychiatry (AACAP) Alan Ezdgli - AACAP Heidi Fordi - AACAP Katia Howlett, Ph.D. - Synergy Enterprises, Inc. Laurel Koepernik - University of California, San Francisco Brendan McEnta - American Society of Addiction Medicine Julie Miller, Ph.D. - RTI International Ellen Robinson, M.H.S. - IQ Solutions Paula Skedsvold, Ph.D. - Federation of Associations in Behavioral & Brain Sciences (FABBS) Isabelle Thibau - Kelly government Solutions Laura Thomas, Ph.D. - Kelly Government Solutions Linda Thomas - Kelly Government Solutions Roy Walker - Synergy Enterprises, Inc. Simon Weaver - BCH Technologies Candace Webb, M.P.H. - Kelly Government Solutions Evelyn Yang, Ph.D. - Community Anti-Drug Coalitions of America (CADCA) Patrick Zickler - SEI, Inc.

Closed Portion of the Meeting - September 5, 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 Pharmacotherapies and Medical Consequences of Drug Abuse, Division of Basic Neuroscience and Behavioral Research, Division of Clinical Neuroscience and Behavioral Research, and 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. For foreign applications, Council provided individual concurrence with the initial scientific reviews. Council also approved one MERIT application and deferred one MERIT extension application. Administrative supplements were approved. Relevant applications were presented to Council for Special Council Review, and Council found them all meritorious and agreed with program assessments.

   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 - September 6, 2012

1. Call to Order

   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 the future 2013 Council meetings: February 5-6, 2013, May 7-8, 2013, and September 9-5, 2013. She acknowledged the work of three retiring Council members, Drs. Nestler, Sorensen, and Walker and thanked them for their service to NIDA.

2. Consideration of the Minutes of Council

   The Minutes of the May 2012 meeting were approved as written.

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

   Dr. Volkow began her report with a tribute to Dr. Toni Shippenberg-Stein who had been the Chief of the Integrative Neuroscience Branch and a Senior Investigator in the intramural program. She noted not only Dr. Shippenberg-Stein's outstanding and numerous scientific contributions but also the many personal qualities that made her much loved by family, friends and colleagues. She will be greatly missed by all who knew her. Dr. Volkow then introduced Dr. Jack Stein, the new Director, Office of Science Policy and Communication (OSPC) and noted how pleased she was that he had returned to NIDA from his position as Chief, Prevention Branch, Office of National Drug Control Policy (ONDCP), to accept this important post at NIDA. She described his previous roles at NIDA, and Council welcomed him. Dr. Volkow then thanked Dr. Susan Weiss for her role as Acting Director, OSPC, and noted that she is now the NIDA Associate Director for Scientific Affairs, OD, and in that position she will be responsible for a variety of NIDA-wide activities. Council also welcomed Dr. Weiss to her new role.

   Dr. Volkow then turned to the NIDA budget, noting that the 2013 President's Budget called for a 0.2% increase over the previous year and that the CR called for a 0.3% increase over the prior year. In both cases, the total NIDA budget would be just over $1,000,000. Dr. Volkow next reported on the continuing activity around the development of a new institute, currently referred to as the National Institute of Substance Use and Addiction Disorders (NISUAD). She noted the timeline, including the plan that, in fall of 2012, the draft scientific strategic plan will be released and that there will then be a public comment period, with December 2012 as the date for recommendations to the NIH Director. In January/February of 2013, aspects of the scientific strategic plan not dependent on reorganization will begin to be implemented, and it is expected that the new institute will stand up in October 2013. Dr. Volkow also noted that many organizations, both federal and non-federal, have been invited to meet with Dr. Tabak to learn about the proposed new institute and to provide input into the new IC's mission; two stakeholders meetings were held over the summer and a number of groups participated. The last item under the topic of "What's New at HHS/NIH" was a report of NIH announcements issued in collaboration with the FDA Center for Tobacco Products. Dr. Volkow described two of these FOAs and invited Council to alert their colleagues to these opportunities.

   There have been several recent NIDA activities and events under each of NIDA's top priority areas of prevention research, treatment interventions and HIV/drugs prevention and treatment. There was a recent NIDA prevention science strategic meeting to develop recommendations for prevention research for the next five years to accelerate discovery and foster the greatest impact on public health. Discussion centered around basic science on human behavior change (type 1 translation) and implementation science (type 2 translation). Themes included transdisciplinary and team science; development of methodologies; big data mining and training scientists to exploit big data sets; new technologies; and learning from the HIV prevention field. Questions pursuant to healthcare reform, training of the next generation of prevention scientists and unexplored or emerging areas for prevention science were also central to the meeting, which Dr. Volkow described as very productive. Dr. Volkow then presented data showing that persistent cannabis users show neuropsychological decline from childhood to midlife and that early long-term cannabis use decreases axonal fibre connectivity. She noted that, taken together, these two studies, though very different in many aspects, lead to the same conclusion that exposure to marijuana during adolescence is detrimental to the brain and, ultimately, to cognitive performance. New FOAs in the prevention arena were also presented.

   In the priority area of treatment interventions, Dr. Volkow noted that there would be a report later in the day from the Council work group that had explored adoption of NIDA's evidence-based treatments in real world settings, and she briefly summarized the major recommendations of that work group. She then pointed to the work of the 2012 Avant-Garde Award for Medications Development awardee, Dr. Gary R. Matyas, who hopes to develop a combination anti heroin/HIV vaccine, building on preclincal data indicating that hapten-based anti-drug vaccines show promise against various drugs, including heroin. The heroin component has been created and is ready for optimization and advanced preclinical testing; the Avant-Garde Award will support this next phase of research and development. Dr. Volkow then described the Grand Opportunity in medications development for substance-related disorders program that is intended to accelerate development of medication for SUD and provide high impact and fast results to advance FDA approval. Two of these short-term cooperative agreements have been awarded, one to Dr. Deepak Cyril D'Souza for study of FAAH-Inhibitor for cannabis dependence, and one to Dr. Ronald Crystal for study of a disrupted adenovirus serotype 5-based anti-cocaine vaccine. Dr. Volkow next presented data from a double blind RCT of N-acetylcsteine in cannabis-dependent adolescents and a study of extended-release mixed amphetamine salts and topiramate for cocaine dependence. She spoke about the importance of combining medications for better outcomes. Dr. Volkow then noted that the FDA has approved the weight management drug Qsymia, which includes topiramate and is a combination drug. She then noted that the NIH Office of Research on Women's Health (ORWH) has funded three applications from NIDA researchers as part of its specialized centers of research on sex differences program; these projects are from Dr. Kathleen Brady, Dr. Marilyn Carroll, and Dr. Sherry McKee, and all are related to treatment. Dr. Volkow concluded her presentation on treatment activities by pointing to a new FOA on the development of minimally-invasive bioassays to support outpatient clinical trials of therapeutics for substance use disorders.

   In the priority area of HIV and drugs, prevention and treatment, Dr. Volkow reported on the International AIDS meeting in July and NIDA's role with the new face of the HIV epidemic. At this meeting, Dr. Volkow talked about the major challenges in this field, which are to seek, test, treat and retain patients, including the central importance of treating substance abusers with ART and treating HIV positive patients for substance abuse. NIDA is developing new therapeutics for IDU so that there will be long lasting medications to improve compliance, medications not based on opioid substitution, as well as vaccines and other immunotherapies. NIDA is also involved in STTR implementation, including substance abuse treatment programs, health care (for example, in STD clinics), the criminal justice system and countries where IDU is a driver of the HIV epidemic. There are three 2012 Avant-Garde awardees for HIV/AIDS research: Dr. David Smith who will be exploring molecular epidemiology for HIV prevention for drug users and other risk groups; Dr. Samuel Friedman who will be exploring prevention of HIV transmission by recently-infected drug users; and Dr. Jeremy Luban who will be studying human genes that influence HIV-1 replication, pathogenesis, and immunity in intravenous drug users. Dr. Volkow also presented three new HIV/AIDS FOAs and noted that a new direction is the interplay of substance abuse and HIV infection on Glial cell functions.

   Other activities have included Dr. Volkow's presentations at a Congressional briefing on women and smoking and a Congressional briefing on HIV/AIDS and drugs. Also, recipients of the 2011 Presidential Early Career Award for Scientist and Engineers were announced, and Dr. Krista Lisdahl was one of 20 NIH recipients of this prestigious award. She is a NIDA grantee studying the effects of physical activity and marijuana use on frontolimbic function in teens. The projects of three 2012 INTEL high school student Addiction Science Awardees were also briefly described. At the Society for Neuroscience (SfN) annual meeting NIDA will present a mini-convention on Frontiers in Addiction Research, and Dr. Volkow listed the symposia that will be presented as well as other tentatively scheduled NIDA-sponsored activities, including the Toni S. Shippenberg Memorial Symposium. The Second Annual National Drug Facts Week will take place in January of 2013, and this continues to be a very successful activity which NIDA is expanding to include NIDA grantees who agree to participate.

   Council thanked Dr. Volkow. There was some discussion about NIDA's work with AIDS- infected African Americans and about the use of the criminal justice system in providing screening and treatment.

4. Medications Trials in Stimulant Dependence: An Update - David McCann, Ph.D., Associate Director, Division of Pharmacotherapies and Medical Consequences of Drug Abuse (DPMCDA)

   Dr McCann presented an update on medication trails in stimulant dependence, summarizing the results of completed trials and the status of ongoing trials. He noted that in January of 2009, all previous NIDA multi-site medication trials (cocaine or meth addiction treatment) and many single-site trials were reanalyzed based on guidance from FDA reviews. He noted the FDA requirements for demonstration of efficacy: a success/failure analysis is required (no group means). "Success" must be clinically meaningful and, preferably, defined by a period of abstinence that lasts until the end of treatment. For the reanalysis of previous trials, "success" was operationalized as abstinence during the last three weeks of treatment, based on urine assay results (at least two urines/week, with 100% clean were required for "success"). Based on the 2009 reanalyses, the most promising medication for cocaine appeared to be vigabatrin and the most promising medication for methamphetamine appeared to be bupropion. Dr. McCann reported that subsequently, a second multi-site trial of bupropion for the treatment of methamphetamine dependence was completed (data were under analysis/unpublished) and a second multi-site trial of vigabatrin for the treatment of cocaine dependence was ongoing.

   Dr. McCann then turned to the issue of medication adherence. He presented data on urine testing for medication in failed trials of modafinil and vigabatrin. In both cases, medication adherence was extremely poor, precluding conclusions about medication efficacy vs. cocaine dependence. He noted that study participants received vigabatrin with observed, in-clinic dosing during a promising trial in Mexico whereas there was no observed dosing in a subsequent failed U.S. trial. The ongoing vigabatrin trial includes observed dosing. Dr. McCann noted that in many past negative trials, there were no attempts to measure medication levels in urine or blood, which raises the possibility that the trials did appropriately evaluate efficacy; some of the medications may have worked if there had been better medication adherence.

   Dr. McCann concluded by listing important lessons learned: 1) do not be left guessing about medication adherence; 2) advance potent compounds that are amenable to sustained release (SR) injection or implant formulation and 3) consider the development of SR injection or implant formulations before Phase II proof of concept testing.

   Council thanked Dr. McCann for his presentation. Discussion included FDA expectations for success, the importance of looking at endpoints other than abstinence, ways NIDA will measure compliance in future studies, the importance of depot implant/injection formulations, the importance of appreciating how patients feel when they take different medications, placebo issues, characteristics of compliant patients, individual differences in response to placebo, reasons for non-compliance, new ways to measure compliance, the role of culture, the importance of requiring endpoints that accurately reflect compliance (e.g., medication concentration in blood or urine) in new NIDA funding opportunity announcements, the challenges of placebo lead-in designs, standards for adherence in efficacy studies compared with effectiveness studies, and, overall, the necessity of measuring and understanding medication adherence in clinical trials.

5. Adoption of NIDA's Evidence-Based Treatments Workgroup Recommendations - Caryn Lerman, Ph.D., Council Workgroup Chair and Mary W. Calkins Professor, University of Pennsylvania

   Dr. Lerman began her report by listing the work group members, and she thanked them as well as NIDA staff for their participation. She then presented the charge given by Dr. Volkow to the work group: 1) determine how effectively the treatment interventions developed, tested and evaluated through NIDA's extramural programs are being used in real world settings; 2) explore barriers for moving from research findings to adoption as standard practice; and 3) consider whether and how the organization of NIDA could best be structured to meet these evolving goals. In addressing how well NIDA's evidence-based treatments are being used, Dr. Lerman presented some evidence that the Work Group considered: 1) a full range of treatment options is not available in many treatment centers; 2) only 8-9% of these treatment centers offer medication treatment; 3) some centers offer detoxification services, but it is not integrated with treatment; and 4) most have drug testing capabilities, but may not monitor routinely for drug abuse. She described some challenges to the effective utilization of NIDA's evidence-based treatments, including the poor integration of these centers with health care systems that are capable of providing comprehensive care, poor uptake of best practices, and inadequate records and reporting systems (although there has been some progress in incorporating substance use screening, brief intervention and referral to treatment (SBIRT) procedures into health care services).

   Dr. Lerman then described barriers to adoption of evidence-based treatments. These include lack of full-time, on site staff to prescribe medications and restrictions on take-home medications; reluctance of some counselors to use medications; privacy concerns (specifically as it relates to 42 CFR Part 2); research focus on intensive, individual-based approaches despite most centers' ability to employ group-level behavioral treatments; lack of infrastructure or industry to market and sell behavioral interventions and social services; and location of substance use disorder treatment in specialty programs that are largely detached from academic research which is suggestive of a deficiency in some researcher's awareness of implementation issues that affect adoption in real world settings. She noted that NIDA can influence many of these barriers. Dr. Lerman then listed some of the ways barriers could be addressed by NIDA's partnering with agencies such as CMS, HRSA, ONDCP, AHRQ, FDA, SAMHSA, and OPM.

   Dr. Lerman then addressed the question of how NIDA's organization could best be structured to address these issues, and she listed five work group recommendations: 1) create a new entity for translation and implementation science in NIDA; 2) establish NIDA "standards" for funding of treatment development research; 3) establish systems-based research networks; 4) expand the implementation science portfolio; and 5) establish a NIDA-based peer-review panel to review research applications that promote adoption of treatments in real world settings. Dr. Lerman stated the Workgroup's definition of implementation science as "the study of methods to promote the systematic uptake of proven clinical treatments, practices, organizational and management interventions into routine practice, and, hence, to improve health".

   She then elaborated on action items for each of the five recommendations. Thus, under recommendation # 1, a new entity in NIDA for translation and implementation science would develop a strategic plan for implementation science; oversee development of criteria for evaluating treatments in development; design FOA for implementation science networks; and leverage existing partnerships for co-development, co-branding and co-funding. For the second recommendation, establishing standards for funding and consideration of treatment development, NIDA would establish, with relevant partners, a task force to outline standards and evaluation criteria with emphasis on adoption, scalability, cost-effectiveness and sustainability; disseminate a white paper about these standards and evaluation criteria to the community; and give funding priority to applications proposing interventions with higher adoption potential. Dr. Lerman noted that the Affordable Care Act (ACA) will lead to changes in health care delivery, with greater emphasis on complex health care systems. Thus, recommendation # 3, establishing system-based networks, would involve shifting efforts from current networks that emphasize addiction treatment programs to those that include health care systems; encouraging development of implementable approaches for screening and treatment; ensuring that networks address effectiveness, adoption, scalability and sustainability of treatments; and forming networks for limited periods of time with a plan to evaluate for renewal or phase out. For recommendation #4, target funding to implementation science, NIDA should establish a forum to identify important topics for new FOAs, develop a plan to seek co-funding by other institutes and non-federal agencies; and engage NIDA Council to review FOAs and monitor progress. Recommendation # 5, establishing a NIDA-based review panel, would be implemented by engaging potential applicants, reviewers and NIDA staff to plan program development; developing applications review criteria to include implementability; and including reviewers who understand practice issues and implementation science in the NIDA-based review committee.

   Dr. Lerman concluded her presentation by noting that NIDA's continued support for the development of new behavioral and medication treatments is commendable and essential; that fundamental changes in treatment delivery systems will be brought about by the ACA and other legislative actions, and that, by better developing and embracing a systems approach, NIDA can facilitate surmounting the barriers to adoption of effective treatments.

   Council thanked Dr. Lerman for her presentation. Discussion included acknowledging the importance of ensuring that treatments are evidence-based and the difficulties of doing so, agreeing that system characteristics must be taken into account so that treatments are adopted, and pointing out that a system of care is not the same as a network. The need to take content, service delivery structure, financing mechanisms and other factors into consideration in order to affect systems was noted. Some opportunities for NIDA to work with other agencies were noted, as was the importance of developing and enhancing partnerships with them to make NIDA research more likely to be utilized. The role of stigma was also noted, as was the need for training for providers at all levels and the need to educate insurance companies and work more effectively with educational institutions. Examples from NCI and other institutes were noted, and information from them helped inform the work group's recommendations. The role of the NIDA CTN in adoption and dissemination and the gap between adoption and effectiveness research were noted, as was the issue of cost, the importance of mandates to purchase services, and research results on SBIRT. It was pointed out that the CTN has recently focused more on mainstream health care systems, including primary care settings and emergency departments, as foci for CTN research and that the CTN has relationships with state and local agencies. Whether it is better to create new networks or optimize extant ones was discussed, and it was also noted that Dr Jack Stein, the new Director of OSPC, brings leadership and experience in implementation and creating partnerships. The importance of integrating NIDA science into CSR review was mentioned, as was the disconnect between substance abuse treatment centers and the medical community.

6. Update on the K99/R00 and Loan Loan Repayment Programs - Susan Weiss, Ph.D., Associate Director for Scientific Affairs, Office of the Director, NIDA

   Dr. Weiss began her overview of the accomplishments of the NIDA Loan Repayment Program by noting that the NIH loan repayment programs are a vital component of our nation's efforts to attract health professionals to careers in research. Briefly, the applicant commits to performing research for at least two years and NIH repays up to $35,000 per year of qualified educational debt and covers the resulting taxes. The goal is to increase the number of biomedical and behavioral research scientists engaging in research vital to the mission and goals of the NIH. Dr. Weiss pointed out that there are five NIH-supported extramural LRPs: clinical research, pediatric research, health disparities research; contraception and infertility research; and clinical research for individuals from disadvantaged backgrounds. NIDA supports the clinical and pediatric research programs. She then defined clinical and pediatric research and noted both NIDA and NIH consistently receives more clinical than pediatric applications each year. Dr. Weiss then showed the LRP success rates from 2002-2012, noting that NIDA's success rates exceed that of NIH for both clinical and pediatric applications. NIDA's LRP success rates for new vs. renewal applications also compares favorably to that of the NIH overall.

   Dr. Weiss went on to describe the subsequent grant and publication activity through 2011 of LRP awardees funded between 2004 and 2008. Among the 313 individuals who LRP awardees, 42% received subsequent NIH grant awards and 97% had scientific publications. The data were further analyzed to examine subsequent grant activity by gender, by program (clinical or pediatric), by degree, and by the type of subsequent grant awarded. She also presented data on LRP awardees with publications by program and degree, and identified the number of publications by LRP awardees. Over 100 out of 313 individuals reported 16 or more publications, while only 8 reported no publications.

   Dr. Weiss then presented a comparison of the NIH top 10% of LRP awardees (by application score) and all NIDA LRP awardees in terms of subsequent grant and publication activity. Again, NIDA awardees compare favorably with the NIH top awardees on both measures. She closed her presentation by showing where online information and application materials could be found and encouraged Council members to share this information with their colleagues and encourage qualified scientists to apply.

   Council thanked Dr. Weiss for her presentation and noted that the LRP has been a very important program for many scientists. The question of why there is limited feedback to the applicants was raised, and Dr. Weiss pointed out that the LRP is not like a traditional grant mechanism but, rather, is a contract mechanism and that different policies about feedback apply. Council commented on the higher success rates for NIDA, when compared to the rest of NIH, though the reasons for this success are not apparent.

7. There were no Public Comments
8. Adjourn

   The 112th meeting of the National Advisory Council on Drug Abuse was adjourned at 12:35 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.