Revised September 2018
Closed Session - May 15th
- Call to Order - Nora Volkow, M.D. Director, NIDA
- Review of Policy and Procedures - Susan Weiss, Ph.D., Executive Secretary, National Advisory Council on Drug Abuse, Director, Division of Extramural Research, NIDA
Council Review of Grant Applications - Nora Volkow, M.D. Director
- Division of Epidemiology, Services, and Prevention Research (DESPR) - Carlos Blanco, M.D., Ph.D., Director
- Division of Therapeutics and Medical Consequences (DTMC) - Ivan Montoya, M.P.H., M.D., Deputy Director
- Division of Neuroscience and Behavioral (DNB) - Rita Valentino, Ph.D., Director
- End of Closed Session
Open Session - May 15th
- Opening and Welcome New Members - Nora Volkow, M.D. Director, NIDA
- NIDA Director's Report - Nora Volkow, M.D., Director, NIDA
- Council Discussion - Council Members
- Lunch Break
- Enhancing Partnerships Between the National Institute on Minority Health and Health Disparities (NIMHD) and NIDA, Eliseo Pérez-Stable, M.D., Director, NIMHD
- The Concept of Patient Centricity and NIDA Research, Elena Koustova, Ph.D., M.B.A., Director, Office of Translational Initiatives and Program Innovations, NIDA
- Concept Clearances? - NIDA Staff
- Public Comments
Minutes - May 15th
The National Advisory Council on Drug Abuse convened its 129th meeting at 9:00 a.m. on May 15, 2018 in Conference Rooms C & D, 6001 Executive Boulevard, Bethesda, Maryland. The closed portion of the meeting held on May 15th was for 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, began at 10:30 a.m. and was also webcast. The Council adjourned on May 15, 2018 at 3:01 p.m.
Council Members Present
Anne Andorn, M.D.
Judith Auerbach, Ph.D.
Laura Bierut, M.D.
Julie Blendy, Ph.D.
Linda Chang, M.D.
H. Westley Clark, M.D., J.D.
Arthur Dean, M.A.
Karl Deisseroth, M.D., Ph.D.
Marie Gallo Dyak
Jay Giedd, M.D.
Kenneth Mackie, M.D.
Lisa Marsch, Ph.D.
Edward Nunes, M.D.
Robert Rancourt, J.D.
Steffanie Strathdee, Ph.D.
Council Members Absent
John Carnevale, Ph.D.
Eric Verdin, M.D.
Nora Volkow, M.D.
Susan Weiss, Ph.D.
Federal Employees Present
Will M. Aklin, Ph.D.
Jinhee Lee, Pharm.D.
Members of the Public Present
Maureen Boyle, Ph.D.—Addiction Policy Forum
Colm Everard, Ph.D.—Kelly Services, Inc.
Shannon Givens—Kelly Services, Inc.
Nahla Hilmi, M.P.H.
Nicole Johnston, M.S.—Global Solutions Network
Jag Khalsa, Ph.D.
Kim LeBlanc, Ph.D.
Phylicia Porter—Kelly Services, Inc.
Victor Prikhodko—Kelly Services, Inc.
Marushka Silveira, Ph.D.
Jamie Sim, M.P.H.
Roy Walker—Synergy Enterprises, Inc.
Kay Woods, M.A., M.P.H.—Community Anti-Drug Coalitions of America
Closed Portion of the Meeting – May 15, 2018
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. Susan Weiss, 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.
Drs. Rita Valentino and Carlos Blanco the Directors of NIDA’s Division of Neuroscience and Behavior, and Division of Epidemiology, Services and Prevention Research, as well as Dr. Ivan Montoya, the Deputy Director of the Division of Therapeutics and Medical Consequences, presented their Division’s assigned and peer reviewed applications for consideration by the Council. For each, Council provided unanimous en bloc concurrence with the initial scientific review. Two Administrative Supplements, two MERIT Awards, and several foreign applications were presented to Council for Special Council Review, and Council concurred with program assessments. The initial reviews of all Trans-NIH Initiatives, including NIH Common Fund, Blueprint and BRAIN applications as well as applications with a secondary assignment to NIDA also received Council concurrence.
Council and staff were recused from the Council meetings during discussion of, and voting on, individual applications from their own institutions or other applications for which there was 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 the room if an application in conflict with that member was acted upon en bloc.
Open Portion of the Meeting – May 15, 2018
Call to Order
Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order and welcomed all attendees. 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 acknowledged the work of three retiring Council members, Drs. Anne Andorn, Laura Bierut and Eric Verdin, thanked them for their service to NIDA, and presented Drs. Andorn and Bierut with a certificate of appreciation (Dr. Verdin was not present.)
She then called attention to future Council meeting dates: May 16, 2018 (CRAN), and September 5, 2018.
Consideration of the Minutes of Council
The Minutes of the NIDA February 2018 meeting were unanimously approved as written.
NIDA Director’s Report – Nora Volkow, M.D., Director, NIDA
Dr. Volkow began by announcing the newly hired director of the Division of Therapeutics and Medical Consequences (DTMC), Kurt Rasmussen, Ph.D. Dr. Rasmussen comes to NIDA from Eli Lilly & Co., where he served as the Senior Research Advisor to their Neuroscience Branch. He brings to NIDA a wealth of knowledge spanning pharmaceutical development as it related to substance use disorders.
Dr. Volkow presented an update on the budget. NIDA’s budget for fiscal year (FY) 2018 is $1.126 billion. NIH received an additional $500 million in FY 2018 funds for research on opioids and non-addictive pain medication. In FY 2017 NIDA spent 38% of its research funding within the Division of Neuroscience and Behavior, 28% in the Division of Epidemiology, Services & Prevention, 15% in the Division of Therapeutics and Medical Consequences, and the remaining budget supported the Center for the Clinical Trials Network, the NIDA Intramural Program, and NIDA’s research support and management activities.
As an overview of recent initiatives across NIH, Dr. Volkow provided a brief update on the All of Us Program, a large-scale research project that will gather data from one million Americans to accelerate research and improve health. By taking into account individual differences in lifestyle, environment, and biology, researchers aim to uncover paths towards delivering precision medicine. NIDA has been very proactive ensuring that individuals suffering with substance use disorders (SUD) are included in this program. She then highlighted the NIH BRAIN Initiative. NIH is mid-way through the 10-year initiative and is shifting its emphasis from technology development to discovery driven science. The current focus of the BRAIN program is on the structure and function of brain circuits, with a long-term goal to make circuit abnormalities the basis of diagnostics, and the normalization of circuit function the target of interventions.
To date, 345 projects and over 500 investigators have received a total of $548.3 million in overall support for the BRAIN high priority research areas. A graphic reflecting the different research areas by level of support from 2014 through 2017 highlights the new emphasis on supporting human imaging and modulation studies. She then showed a bar graph reflecting the BRAIN Initiative awarded and committed funds as of FY 2017, as well as a continuum of lifetime support through FY 2026 that has been authorized by the 21st Century Cures Act. She added that NIH is continuing its search for the BRAIN Initiative Director.
Dr. Volkow summarized several recent NIDA activities and events including an overview of the Cannabis laws in the U.S. Marijuana laws differ state by state. Twenty-nine states have legalized medical marijuana, along with the District of Columbia, Guam, and Puerto Rico. Each state varies on the allowable conditions and routes of administration, dispensaries or home growth and registries, and testing or regulatory requirements. In addition, states with recreational laws vary on marketing, product labeling, distribution, and taxation. The NIDA Cannabis Policy Research Workgroup recently submitted a report outlining a policy research agenda to advance science on the causes and consequences of cannabis use and addition. This workgroup identified areas of research ideas that fell into five broad topic areas: 1) Cannabis Use; 2) Epidemiology; 3) Health and Social Consequences; 4) The Structure, Behavioral, and Conduct of the Industry; and 5) Prevention and Treatment. The full report is available online at: https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/nacda_cannabis_policy_research_workgroup_report_feb_2018.pdf
Dr. Volkow continued by describing current activities to establish measures and metrics of intoxication and impairment when using cannabis. NIDA is working with the Centers for Disease Control and Prevention (CDC) and other federal partners on common surveillance measure to evaluate the impact of changing laws. In addition, the Division of Epidemiology, Services and Prevention Research (DESPR) has expanded its research portfolio covering the implications of cannabis policy changes. Proposed plans are to convene a meeting on measures to define a “standardized dose,” to expand research on cannabis policy by adding it as a priority area to the Drug Abuse Topics (DAT) of Interest website, to expand interest on intersections with opioids for pain treatment, and to include NIDA’s international priorities by taking advantage of changes occurring in Canada, Uruguay, and elsewhere. Dr. Volkow then shared two recent SBIR program funded projects. 1) A system for the Specification of Acute THC Impairment using Validated Algorithms (SATIVA). It is a smartphone sensor data collection application that can be used by law enforcement to measure psychophysiological and physiological markers and create an algorithm that can be used as an indication of the level of intoxication. Another device is the Cannabis Impairment Detection Application (CIDA). It combines battery-powered hardware with a sensor placement system that provides a lightweight, easy-to-apply method to acquire and analyze up to 20 channels of high-quality EEG, ECG, and accelerometry data.
Dr. Volkow then provided updates on the Adolescent Brain Cognitive Development (ABCD) Study. Since its launch in September 2015, the ABCD Consortium has recruited 9,251 children. The curated data, including assessment domains and computational analysis pipelines, was released in February 2018 and included the first 4,500 participants. A Funding Opportunity Announcement (FOA): RFA-DA-19-006 was issued in March 2018 requesting applications that will support creative educational activities with a primary focus on courses for skills development that will allow participants to explore the hands-on use of ABCD data, through cooperative or competitive approaches. Dr. Volkow also described a potential future project similar to the ongoing ABCD longitudinal study, which might monitor populations from birth to 10 years of age.
Dr. Volkow addressed the opioid health crisis. A (CDC) map of the United States, comparing overdoses in 1999 vs. 2016, illustrates the tremendous increase in overdoses across the country. Similarly, comparing 2017 with 2015, overdose rates increased 22%, predominantly driven by fentanyl, which has much higher potency and profitability in the illegal market than heroin. The NIH Opioid Research Initiative is expected to enhance related research to help address the opioid crisis. Three major research priorities will be addressed: pain management as it relates to prevention of opioid use disorders (OUD) and discovery of alternative therapies; opioid addiction treatment; and overdose reversal. A recent study from Stanford University by Stoeber et al. (“A genetically encoded biosensor reveals location bias of opioid drug action.” Neuron. 10 May 2018; 10(1016) identifies important distinctions between the opioids naturally made by the brain, and therapeutic opioids. The researchers hypothesize that therapeutic and/or abused opioids distort the normal time and spatial sequence of the mu-opioid receptor, a member of the G protein-coupled receptors (GPCRs), activation and signaling. This might explain the mechanism of the undesired side effects of opioid medications and may suggest new avenues for designing pain management agents with decreased addictive characteristics.
NIDA, in collaboration with the National Center for Complementary and Integrative Health (NCCIH) have issued a new FOA “Exploring Epigenomic or Non-Coding RNA Regulation in the Development, Maintenance, or Treatment of Chronic Pain (R61/R33 Clinical Trial Optional) PAR-18-742.” The goal is to support research that investigates the role of epigenetic or non-coding RNA regulatory pathways in the development, maintenance, or treatment of chronic pain to expand knowledge that can be translated to identify non-addictive pain medications and pain biomarkers.
To further address research priorities relevant to opioid addiction treatment and overdose reversal, continued discovery and use of Medication Assisted Treatment (MAT), which has been shown to decrease opioid use, opioid-related overdose deaths, criminal activity, and infectious disease transmission, is indicated. MAT can also improve social functioning, and retention in treatment. However, the three approved MATs on the market today are highly underutilized. Strategies are needed to expand access to MAT in both the healthcare system and the criminal justice system. Relatedly, Heidbreder et al. presented at the College on Problems of Drug Dependence (CPDD) conference, 2017 on use of Sublocade (Buprenorphine Extended Release), a once-a-month injectable shown to increase the length of abstinence (opioid-free) using urine samples from 5 to 24 weeks. Another MAT on the market is CAM2038, a subcutaneous extended release Buprenorphine that can be injected monthly and which has also been shown to increase the rate of abstinence. These medications help with compliance, as well as maintaining stable plasma concentrations to decrease relapse rates and negative side effects. The FDA has also recently approved the use of lofexidine for opioid withdrawal. It is an alpha-2 adrenergic agonist that helps minimize withdrawal effects among individuals rescued with Naloxone.
Dr. Volkow briefly described a joint FDA and NIDA initiative to seek patient perspectives on opioid therapy, led by Dr. Koustova, Director of the Office of Translational Initiatives and Program Innovations, NIDA, who provided more details in the afternoon Council open session. Dr. Volkow then introduced the new NIH Initiative to Address the Opioid Crisis: HEAL (Helping to End Addiction Long-term). HEAL is a collaborative, cross cutting research initiative effort that spans basic to behavioral studies, it fosters innovative partnerships across agencies, sectors, and organizations to ensure rapid progress, advances national priorities for pain and addiction research, and adds $500 million to the current FY 18 funds, for a total of $1.1 billion. Some of the priorities for the HEAL Initiative are related to prevention and treatment. The goals for prevention are to better understand the origins and nature of chronic pain, to develop new non-addictive treatments for pain, to build clinical trial network for chronic pain, and to enhance precision pain management. The goals for treatment are to improve therapeutic approaches to addiction, to evaluate treatments and consequences of neonatal opioid withdrawal syndrome (NOWS), and to optimize effective treatments through pilot demonstration projects.
Dr. Volkow discussed another of NIDA’s priority themes, HIV and Drug Use. She summarized a study that looked at the predictors of linkage to HIV care after release from prison or jail. Loelinger et al.’s (Predictors of linkage to HIV care and viral suppression after release from jails and prisons.” Lancet HIV. 2018 Feb; 5(2): e96-106) paper showed that only 21 percent of those released from prison access treatment for HIV upon release. This could be due to state laws affecting health insurance coverage, and whether health insurance coverage is suspended or canceled after incarceration. NIDA expects to expand its research portfolio in the criminal justice arena.
NIDA has recently released RDA-DA-19-004: Coordinating Center to Support NIDA Rural Opioid HIV and Comorbidity Initiative (U24-Clinical Trial Not Allowed). The purpose of this FOA is to fund a single interdisciplinary Coordinating Center to centralize support of the rural opioid initiative, and is to be administered by NIDA and co-funded by the CDC, Substance Abuse and Mental Health Services Administration (SAMHSA), and Appalachian Regional Commission (ARC). The application receipt date is August 15, 2018.
Dr. Volkow concluded her presentation by sharing a new webpage whose theme and design is led by Susan Weiss, NACDA Executive Secretary and Director, Division of Extramural Research, called the NIDA Topics of Special/Continuing Interest (DAT). In an effort to limit the number of Program Announcements that NIDA issues, while continuing to effectively inform potential applicants about emerging and continuing areas of research priorities, the Drug Abuse Topics (DATs) of interest will consolidate the themes of existing funding opportunity announcements, to encourage topic-specific applications within areas of emerging interest to the Institute. Dr. Volkow encouraged recommendations for additional investigator-initiated ideas, projects and applications in topic areas not listed on the DAT page.
Council thanked Dr. Volkow for her presentation and commended NIDA on rising to the challenge of addressing the opioid crisis. Among comments, concerns were expressed regarding the limited support for some types of HIV related research, despite the additional expected funding from the NIH Opioid Research Initiative. Dr. Volkow assured Council that high priority HIV research applications will continue to be supported if they address OAR and/or NIDA priorities. Additional comments included recommendations to further train and support investigators to more effectively provide their data and analyses to inform prevention related research, initiatives, and policies.
Enhancing Partnerships Between the National Institute on Minority Health and Health Disparities (NIMHD) and NIDA—Eliseo Pérez-Stable, M.D., Director, NIMHD
Dr. Pérez-Stable began his presentation with an overview and history of NIMHD, which was first established as an Office under the NIH Director and the HHS Secretary Louis W. Sullivan, M.D. in 1990. In 2000, it transitioned into a Center through legislation introduced by Representative Louis Stokes (D-OH), and was established as an Institute in 2010 as part of the Affordable Care Act. NIMHD has two major focus areas, minority health and health disparities. Minority Health research emphasizes health determinants that lead to specific outcomes within a minority group and in comparison, to others. Race and ethnic minorities share a social disadvantage and/or are subject to discrimination as a common theme. Dr. Perez-Stable provided a list of the White House's Office of Management and Budget’s (OMB) standards for race and ethnicity data for federal agencies. Health disparity populations defined by NIHMD include racial/ethnic minorities as defined by OMB, less privileged socio-economic status, underserved rural residents, and/or sexual gender minorities.
Dr. Pérez-Stable discussed four mechanisms leading to health disparities. 1. Individual behaviors, social determinants, and beliefs: response to chronic stress, racism, childhood adverse conditions, food insecurity, witness to or victim of violence, immigrant stress, and limited English proficiency; 2. Biological processes and genetics including earlier age of onset, gene variants, metabolic differences, susceptibility, faster progression or greater severity, brain networks, microbiome, and extracellular RNA; 3. Physical and cultural environment, including place, social system, neighborhood, green space, infrastructure, family, social interactions, and community cohesion; and 4. Clinical events and health care, including differential treatments, poor communication, adverse events to medications, progression of disease, access, use/abuse of appropriate services, and end of life care. NIMHD generated a research framework based on the mechanisms, domains of influence and levels of influence, as a guide for the extramural community to classify their research. NIMHD supports three areas of research: clinical and health services research; integrative biological and behavioral sciences; and community health and population sciences. Inclusion of diverse populations and minorities in clinical studies is an important and separate domain from the science, and relevant discoveries can be made through the inclusion of diverse populations.
Dr. Pérez-Stable spoke about NIMHD’s future research directions, including supporting multi-level interventions to address health disparities and improve minority health, identifying mechanisms that lead to disparities, assessing specific communication strategies between patients-clinicians to maximize trust, and implementing structural change to modify behavior. He also provided a list of NIMHD research funding opportunity announcements (FOAs) for fiscal year 2018, including one issued in collaboration with NIDA, PAR-18-747: Addressing the Challenges of the Opioid Epidemic in Minority Health and Health Disparities Research in the U.S. (R01 Clinical Trial Optional).
Dr. Pérez-Stable presented updates on opioid use disorders and health disparities, although there is a relative lack of available data. While overdose related deaths in Latinos, Asians and African Americans are lower than in Caucasians, rates are rising, especially among American Indians/Alaska Natives. Cocaine is the major drug associated with overdoses among African Americans. It is possible that minorities are less likely to be prescribed controlled substances; there remains limited data on the use of medication assisted therapy in minorities, and regarding consequences to newborns of mothers with addiction disorders.
He then addressed another NIDA supported research topic, tobacco abuse. According to the National Health Interview Survey on Cigarette Smoking in the U.S. from 2015 data, Morbidity and Mortality Weekly Report-November 11, 2016. 65(44); 1205-1211, American Indian/Alaska Native women, followed by African American males, have high rates of cigarette smoking. Overall, there is a trend toward lower prevalence rates, and lighter and non-daily smoking, although data regarding cessation interventions are lacking; second-hand smoke exposure seems to affect African American and poor populations disproportionately, and biological factors may also affect lung cancer.
Dr. Perez-Stable closed his presentation by summarizing some of the data from the Hispanic Community Health Study/Study on Latinos, a genome-wide association study of heavy smoking. Genetic associations with smoking behavior was conducted among 12,741 Latinos smokers and 5,119 never-smokers. The CHRNA5 locus, which encodes the alpha 5 cholinergic nicotinic receptor subunit, is highly and significantly correlated with heavy smoking. In addition, several loci on chromosomes 2 and 4 achieved genome-wide significance for association with non-daily smoking, although confirmation of these associations was challenging for the small number of Hispanic samples.
Dr. Volkow and Council members thanked Pérez-Stable for his presentation. Multiple comments related to the emergence of cocaine and methamphetamine use among racial and sexual minorities were discussed. Dr. Volkow assured Council that NIDA is addressing the issue of prevention, and assured that NIDA continues to support research on drugs other than opioids. Dr. Pérez-Stable encouraged Council members to include under-represented minorities in their research studies, as population-based correlations may be discovered that lead to improved outcomes.
The Concept of Patient Centricity and NIDA Research—Elena Koustova, Ph.D., M.D., Director, Office of Translational Initiatives and Program Innovations, NIDA
Dr. Elena Koustova opened her presentation with this statement “Prescription drugs and devices remain the only high-value products created with little or no input from the individuals who use them” and the definition of patient centricity. Patient centricity is both an attitude and an approach resulting in the routine involvement of patients throughout the lifecycle of biomedical product development, including research prioritization, product development, trial design, regulatory approval, access, reimbursement, and treatment decisions. This concept moves patients from being trial subjects or recipients of services (transaction-based), to being consistent collaborators and development partners (relationship-based). It also shifts the paradigm from indirectly obtaining patients’ needs and preferences using healthcare providers (HCPs) and key opinion leaders (KOLs) as proxies (“what would patients say?”) to understanding the patient journey and experience first-hand from patients (“what did patients say?”). Current legislature supports the patient centricity concept: Patient engagement is among the bio- and pharmaceutical companies’ top priorities in the Prescription Drug User Free Act (PDUFA) reauthorization. In addition, an entire section of the 21st Century Cures Act, H.R.6; the Food and Drug Administration’s (FDA) Safety and Innovation Act (FDASIA); as well as the FDA’s Patient-Focused Drug Development initiative part of the PDUFA V support patient centricity.
NIDA, with the leadership of Dr. Volkow, is one working to incorporate patient feedback into our research agenda. In July 2017, NIDA, with the help of the Addiction Policy Forum patient advocacy group, published a Request for Information (RFI): Patient and Family Needs and Requirements to be Addressed by the Small Business Programs of the National Institute on Drug Abuse. The goal was to understand patient and family needs that could be addressed by NIDA’s Small Business Technology Transfer (STTR) and Small Business Innovation Research (SBIR) programs. The objectives were to identify unaddressed needs, identify products and programs currently used and the motivations for using them, assess accessibility of current treatment, prevention, and education programs, identify points of dissatisfaction with accessed products and programs, and to identify what science can do for the patients and customers. Three hundred thirty-five responses were received in the 6-week period, with family members having the highest rate of response at 84.5% and the average length of the responses being 1 page single spaced. Textual data was analyzed and the highest percent of responses related to lack of treatment availability for addiction; the need for treatment to encompass a full continuum from detox to recovery programs; and the need for compassion and training among the staff that provide help to patients and their families. The data was further parsed by focus area, with treatment having the highest unique feedback rate, and within that, the sub-focus areas that were identified were the need for education, policy, and system change.
Dr. Koustova then described another patient-centric project promoted jointly by NIDA and the FDA, the Patient-Focused Drug Development (PFDD) Initiative. Part of the FDA commitments under the fifth authorization of the PDUFA V includes obtaining patient perspectives on specific diseases and their treatments, as well as, perspectives on specific symptoms, differences between symptoms, and their impact on health-related quality of life. The goal of the PFDD Initiative is that patients will be able to provide context for benefit-risk assessments and input to review decisions, and to aid in the development of new assessment tools, study endpoints, and risk communications. This input, in turn, can inform the FDA’s decisions and oversight during drug developments and during review of a marketing application. Recently, the FDA accepted and offered to lead a PFDD meeting for patients suffering from opioid use disorders, jointly with NIDA, the Addiction Policy Forum, and others. Dr. Koustova thanked her staff for their successful efforts with organizing the event logistics.
The OUD PFDD meeting took place on April 17, 2018. Two discussion topics were emphasized: Health effects and daily impacts of OUD; and current approaches to treatment of OUD. The FDA released its first Guidance for Industry-Opioid Dependence: Developing Depot Buprenorphine Products for Treatment, on April 20th. The guidance also describes Novel Efficacy Endpoints, and encourages stakeholders to participate and evaluate new end points: “… there is great public health interest in assessing additional, clinically meaningful endpoints such as reduction in hospitalizations, emergency department visits, overdose, and death, as well as improvements in the ability to resume work, school, or other productive activity. While understanding these outcomes would be highly valuable, the Agency recognizes that evaluating these outcomes could require larger trials than those usually conducted for marketing approval. However, use of such endpoints could provide the basis for additional claims for approve buprenorphine products.”
In conclusion, Dr. Koustova, said regarding the path from PFDD public meetings to clinical study endpoints, that the PFDD meetings alone will not address gaps in information on the patient perspective. A next step is to bridge from PFDD-type meetings to methodologically sound, fit-for-purpose tools to systematically collect key information about patients’ experience, including the burden of disease, benefit and the burden of therapy. The FDA will develop a series of four guidance documents describing in a stepwise manner how stakeholders can collect and submit information from patients and caregivers to be used for medical product development and regulatory decision making.
Dr. Volkow and Council members thanked Dr. Koustova for her presentation. One recommendation from Council was to ensure that diagnosis guides patients into the appropriate treatment, and that that patients are empowered with a list of questions, and/or knowledge to help identify suitable treatment for their respective diagnosis.
Concept Clearances – NIDA Staff
Two concepts received Council clearance.
Jonathan Pollock, Ph.D., Chief, Genetics, Epigenetics, and Developmental Neuroscience Branch, Division of Neuroscience and Behavior (DNB) presented: Community Resource: Post-Mortem Brain Resources for Exploring HIV Compartments in Individuals with Opioid Use Disorders (OUD).
Latent HIV infection can occur in a variety of cell types and tissues. The brain is one of these compartments, but the extent to which substance use impacts the establishment and maintenance of latent HIV infection is poorly understood. Post-mortem brains are needed to make valid comparisons for the effects that HIV has on the brain epigenome as well as determining how drugs affect HIV latent infections in the central nervous system. Thus, suitable brain specimens (HIV minus, with (100) Opioid+/HIV- and 100 Opioid +/HIV+ per year) are proposed to be collected as part of this initiative. Emphasis will be placed on collecting post-mortem brains from infected and uninfected subjects who suffered from OUD:The proposed research resource will help support research into:
- How do drugs of abuse affect the establishment and maintain latent HIV infection in different cell types and compartments of the central nervous system.
- How HIV infection together with drugs of abuse affects epigenetic changes such as methylation, chromatin modifications, eQTLs, and the 3D genome. The use of control tissue allows investigators to distinguish the effect of HIV infection from those produced by drugs of abuse.
Kathy Etz, Ph.D., Director, Native American Program, and Sara Q. Duffy, Ph.D., Associate Director for Economics, Division of Epidemiology, Services and Prevention Research (DESPR) presented: Responding to Opioid Use Disorders (OUD) in Tribal Communities in the Context of SAMHSA Tribal Funding.
American Indians and Alaska Natives (AI/AN) have been disproportionately affected by the opioid crisis, second to or equal to Caucasians in the rate of overdose deaths and diagnosis for OUD. AI/AN had the highest drug overdose death rates in 2015 and the largest percentage change increase in the number of deaths from 1995 to 2015. Despite this health burden, few studies of the prevention or treatment of OUD have been conducted with AI/AN.
Tribes and tribal organizations have both unique opportunities for and barriers to responding to the opioid epidemic. The status of tribes as sovereign nations uniquely positions them to use tribal policymaking in response to the opioid crisis. This provides an opportunity for research and practice partnerships to showcase how tribal responses, including those focused on prevention, treatment or multi-level, community wide responses, can address the risks for opioid use, improve treatment outcomes and reduce overdose deaths and addiction. Some unique barriers exist as well, particularly related to the implementation of medication assisted treatment (MAT), such as no published outcome studies of MAT nor studies indicating the availability of this treatment for AI/AN, the concern that using MAT is substituting one drug for another, the cultural incongruency of standard treatment approaches, distance to treatment, insufficient funding, and stigma. Many treatment programs do not reflect the AI/AN value for a holistic approach to recovery that includes bringing mental, emotional, physical and spiritual aspects of health into balance, nor do they incorporate traditional practices or other culturally appropriate strategies.
Recent funding to the Substance Abuse and Mental Health Services Administration (SAMHSA) addresses one barrier for AI/AN communities; insufficient funding for strategies to combat OUD. In their 2018 budget allocation, SAMHSA is required to provide $50,000,000 for Tribes and Tribal organization to respond to OUD, including prevention and treatment; an FOA is in development.
The goal of this FOA is to solicit applications from researchers partnering with AI/AN communities, tribes or tribal organizations to use community based participatory research approaches to develop and assess culturally appropriate interventions supported within the context of expanded SAMHSA funding. This research will help to identify the most efficacious strategies for preventing and/or treating OUD in tribal communities, where unique culture, structures for and access to health care, and beliefs about treatment all impact OUD outcomes. Specific to treatment, this research will help to identify and address barriers to appropriate treatment and hasten the availability of clinically appropriate MAT and other relevant strategies. Further, it will help to elucidate how cultural grounding or adaptation can improve treatment efficacy. Given that unique barriers to treatment for this population include distance, this research could test whether the use of long acting MAT (Sublocade, Vivitrol, Probuphine) helps in making MAT available to remote communities, helps reduce stigma, or otherwise improves treatment use and outcomes for AI/AN.
AdjournThe 129th meeting of the National Advisory Council on Drug Abuse was adjourned at 3:01 p.m.
I hereby certify that the foregoing minutes are accurate and complete.
Nora D. Volkow, M.D.
National Advisory Council on Drug Abuse
Susan Weiss, 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.