Minutes of the 154th Meeting of the NATIONAL ADVISORY COUNCIL ON ALCOHOL ABUSE AND ALCOHOLISM
DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
154th Meeting of the
NATIONAL ADVISORY COUNCIL ON ALCOHOL ABUSE AND ALCOHOLISM
May 12, 2020
The National Advisory Council on Alcohol Abuse and Alcoholism (NIAAA) convened for its 154th meeting at 1:01 p.m. on Tuesday, May 12, 2020, via Webex videoconference and NIH Webcast. The Council met in closed session from 12:30 p.m. to 12:50 p.m. to review grant applications and cooperative agreements. Dr. Abraham Bautista, Director, Office of Extramural Activities, presided over the Council’s review session, which, in accordance with the provisions of Sections 552b(C)(6), Title 5, U.S.C., and 10(d) of Public Law 92-463, excluded the public for the review, discussion, and evaluation of individual applications for Federal grant-in-aid funds. The closed session recessed at 12:50 p.m.
Council Members Present:
Louis E. Baxter, M.D.
Jill B. Becker, Ph.D.
Daniel J. Calac, M.D.
Christopher S. Carpenter, Ph.D.
Alex M. Dopico, M.D., Ph.D.
Robert J. Hitzemann, Ph.D.
Constance M. Horgan, Sc.D.
Beth Kane-Davidson, LCADC, LCPC
Charles H. Lang, Ph.D.
Mary E. Larimer, Ph.D.
Laura E. Nagy, Ph.D.
Laura Elena Odell, Ph.D.
Scott J. Russo, Ph.D.
Vijay H. Shah, M.D.
Susan M. Smith, Ph.D.
Edith Vioni Sullivan, Ph.D.
NIAAA Director and Chair: George F. Koob, Ph.D.
NIAAA Deputy Director: Patricia Powell, Ph.D.
Executive Secretary: Abraham P. Bautista, Ph.D.
Senior Staff: Vicki Buckley, M.B.A.; Ralph Hingson, Sc.D.; M. Katherine Jung, Ph.D.; Raye Litten, Ph.D.; Antonio Noronha, Ph.D.; and Bridget Williams-Simmons, Ph.D.
Other Attendees at the Open Session:
Approximately 22 observers were present on Webex and another 50 viewed the NIH live webcast, including representatives from constituency groups, liaison organizations, NIAAA staff, and members of the general public.
Call to Order
NIAAA Director George Koob, Ph.D., called the open session of the Council meeting to order at 1:01 p.m. on Tuesday, May 12, 2020.
Director’s Report
Dr. Koob highlighted key recent NIAAA activities, referring to the written Director’s Report, which was distributed to Council members.
Staff Transitions:
Dr. Koob welcomed the following new staff to NIAAA’s Division of Intramural Clinical and Biological Research (DICBR): Elma Aflaki, Ph.D., Staff Scientist, Laboratory of Molecular Signaling; Michelle Antoine, Ph.D., Basic Tenure-Track investigator and 2019 NIH Distinguished Scholar; Salma Majid, Ph.D., Staff Scientist, Laboratory of Neurogenetics; and Commander (CDR) LaToya Sewell, MSN, FNP-BC, of the United States Public Health Service, Office of the Clinical Director. He announced the following internal appointments and promotions within DICBR: Raouf Kechrid, D.V.M., Ph.D., Facility Head of the Office of Laboratory Animal Science; Peter Menza, Ph.D., Research Fellow in the Laboratory of Neuroimaging; and Vijay Ramchandani, Ph.D., tenured Senior Investigator and Chief of the Section on Human Psychopharmacology. He also noted the departure of Gabriela Coello, former Administrative Officer, who transferred to the National Cancer Institute (NCI).
Fiscal Year 2020 Budget:
NIH received $41.6 billion for Fiscal Year (FY) 2020, a $2.3 billion increase from FY19. This funding includes allocations for the Helping to End Addiction Long-term (HEAL) Initiative; the 21st Century Cures Act; the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative; and research on influenza. It also continues support for the Gabriella Miller Kids First Act Pediatric Research Initiative. NIAAA received $545.4 million, a $19.8 million increase from FY19. The FY21 budget is under development.
Role of Alcohol in the COVID-19 Pandemic:
Alcohol misuse leads to impaired immune function, heightening susceptibility to viral pathogens and pneumonia. In particular, chronic alcohol consumption increases the risk for Acute Respiratory Distress Syndrome (ARDS), resulting in the need for mechanical ventilation, a prolonged intensive care unit stay, and higher incidence of mortality. Half of those with ARDS have a history of alcohol misuse. Other key elements affecting NIAAA research are the social isolation and stress resulting from physical distancing imposed by the COVID-19 pandemic, conditions that may lead to greater alcohol misuse as a coping mechanism. Physical distancing during the pandemic also increases the need for telehealth and virtual meeting options for individuals seeking treatment or in recovery from alcohol use disorder (AUD).
NIAAA’s Response to COVID-19 Pandemic:
In response to the pandemic, NIAAA has created a new landing page on its website with links to an updated NIAAA Treatment Navigator with COVID-19 telehealth messages; updates to the Alcohol Policy Information System (APIS) that include new information about state level alcohol-related COVID-19 policies; a Fact Sheet on “Alcohol and Physical Distancing”; and the Director’s blog entry titled “Alcohol poses different challenges during the COVID-19 pandemic.” Other efforts include ongoing press engagement and social media outreach (including Twitter chats with the American Society on Addiction Medicine [ASAM] and the American Psychological Association [APA]). In addition, NIAAA is collecting data on apparent per capita alcohol consumption during the pandemic.
COVID-19 Funding Opportunities:
NIAAA and NIH have a number of pending Notices of Special Interest (NOSIs) related to COVID-19. These include the Availability of Administrative Supplements and Competitive Revision Supplements on Coronavirus Disease 2019 (COVID-19) within the Mission of NIAAA (NOT-AA-20-011). In addition, the following NIH-wide NOSIs have NIAAA participation: Availability of Administrative Supplements and Urgent Competitive Revisions for Research on the 2019 Novel Coronavirus and the Behavioral and Social Sciences (NOT-OD-20-097); Availability of Administrative Supplements and Urgent Competitive Revisions for Research on Stress Management in Relation to Coronavirus Disease 2019 (COVID-19) (NOT-AT-20-011); Availability of Administrative Supplements and Urgent Competitive Revisions for Mental Health Research on the 2019 Novel Coronavirus (NOT-MG-20-047); Availability of Administrative Supplements and Revision Supplements on Coronavirus Disease 2019 (COVID-19) (NOT-AG-20-022); Administrative Supplements for NIH grants to Add or Expand Research Focused on Maternal Mortality (NOT-OD-20-104); Competitive and Administrative Supplements for the Impact of COVID-19 Outbreak on Minority Health and Health Disparities (NOT-MD-20-019); and Availability of Urgent Competitive Revisions and Administrative Supplements For Research on Biological Effects of the 2019 Novel Coronavirus on the Nervous System (NOT-NS-20-051).
COVID-19 science-focused NOSIs (including NOT-AA-20-011) are linked to PA-18-591 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements to request additional funding to increase or preserve the parent award's overall impact within the original scope of award or expand one of the existing specific aims; and PA-18-935 - Urgent Competitive Revision to Existing NIH Grants and Cooperative Agreements to request additional funds during the current project period for new or additional activities that reflect an expansion of the scope of the grant-approved activities, e.g., adding a new specific aim on the effects of alcohol and COVID-19 on the liver.
Dr. Koob also reported that NIH is providing administrative supplements to existing grants for activities disrupted by COVID-19. i.e., unexpected increases in cost and hardships. All Administrative Supplement applications for activities disrupted by COVID-19 must be submitted through the parent administrative supplement NOFO (PA-18-591). He responded affirmatively to a question from Susan Smith, Ph.D. about whether extensions to existing Kirchstein fellowship awards would be included in this category.
NIAAA
Notice of Funding Opportunities (NOFOs):
New NIAAA NOFOs include a Consortium on the Neurobiology of Adolescent Drinking in Adulthood (U01 Clinical Trial Not Allowed; U24 Clinical Trial Not Allowed) (RFA-AA-20-003; RFA AA 20-004; RFA AA-20-005); Impact of Alcohol on the Onset and Progression of Alzheimer’s Disease and Its Related Dementias (R01 - Clinical Trial Optional) (RFA-AA-20-006); and Medications Development for the Treatment of Alcohol Use Disorder (AUD) or Alcohol-Related Organ Damage (AROD), or the Combination of AUD and AROD (U01 Clinical Trial Optional) (RFA-AA-20-007).
NIAAA Participation in NIH-wide NOFOs:
NIAAA is currently participating in over 20 NOFOs and NOSIs; a full listing may be found in the written Director’s Report. Dr. Koob highlighted the following opportunities: BRAIN Initiative: Exploratory Team-Research BRAIN Circuit Programs (U01 - Clinical Trials Optional) (RFA-NS-20-029); Helping End Addiction Long-term (HEAL) Supplements to Improve the Treatment and Management of Common Co-occurring Conditions and Suicide Risk in People Affected by the Opioid Crisis (NOT-MH-20-025); and National Cooperative Drug/Device Discovery/Development Groups for the Treatment of Mental or Substance Use Disorders or Alcohol Disorder (U19 - Clinical Trial Optional) (PAR-20-119).
NIAAA Collaborations with Other Institutes/Centers (ICs):
NIAAA has prioritized working with other ICs on issues of mutual concern, such as: Research on health effects, e.g., fatty liver disease (National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK]) and alcohol and cancer (NCI); aging research, including alcohol and progression of dementias (National Institute on Aging [NIA]); pain research, i.e., the HEAL Initiative; neuroscience research across NIH, including the NIH Blueprint for Neuroscience Research, BRAIN Initiative, and intramural collaboration via the NIH Center for Compulsive Behavior; Collaborative Research on Addiction at NIH (CRAN), i.e., the Adolescent Brain and Cognitive Development (ABCD) study and the HEALthy Brain and Child Development Study.
Supporting the Next Generation of Alcohol Researchers:
Since 2014, NIAAA has steadily increased the number of training and career development awards it supports. F and T training positions increased from 269 in 2014 to 325 in 2019 and career awards increased from 93 to 124 over the same period.
Research Highlights:
Dr. Koob presented highlights of NIAAA-funded studies, including:
“Fetal Alcohol Spectrum Disorder Predisposes to Metabolic Abnormalities in Adulthood” was published in The Journal of Clinical Investigation (2020 Mar 23; pii: 132139. doi: 10.1172/JCI132139) by O Weeks, GD Bossé, IM Oderberg, S Akle, Y Houvras, PJ Wrighton, K LaBella, I Iversen, S Tavakoli, I Adatto, A Schwartz, D Kloosterman, A Tsomides, ME Charness, RT Peterson, ML Steinhauser, PK Fazeli, and W Goessling. Analysis of patient health data revealed that prenatal alcohol exposure (PAE) is a risk factor for developing features of metabolic syndrome in adulthood. Using a zebrafish model of PAE, researchers examined the biological and molecular connections between these metabolic abnormalities and PAE. PAE was associated with obesity, fasting hyperglycemia, increased abdominal fat, and abnormal liver development in adult fish challenged with a high-fat, high-cholesterol diet. This study has implications for prevention strategies among individuals with prenatal alcohol exposure.
“Kcnn2 Blockade Reverses Learning Deficits in a Mouse Model of Fetal Alcohol Spectrum Disorders” was published in Nature Neuroscience (2020 Apr; 23(4):533-543. doi: 10.1038/s41593-020-0592-z. Epub 2020 Mar 16) by S Mohammad, SJ Page, L Wang , S Ishii, P Li, T Sasaki, A Basha, A Salzberg, Z Quezado, F Imamura, H Nishi, K Isaka, JG Corbin, JS Liu, Y Imamura Kawasawa, M Torii, and K Hashimoto-Torii. Alcohol-induced activation of heat shock factor 1 (HSF1) leads to epigenetic changes in nearly 100 genes. This study tested one change, increased expression of a small-conductance calcium-activated potassium channel, Kcnn2, in the motor area of the cerebral cortex. The study demonstrated that increased Kcnn2 expression correlated with deficits in motor skill learning caused by prenatal alcohol exposure that were mitigated by pharmacological blockade of Kcnn2. These results provide early evidence for Kcnn2 blockade as a potential pharmacotherapy for FASD-related learning disabilities.
“Concurrent Prenatal Drinking and Smoking Increases Risk for SIDS: Safe Passage Study Report” was published in EClinicalMedicine (2020 Jan 20;19:100247. doi: 10.1016/j.eclinm.2019.100247) by AJ Elliott, HC Kinney, RL Haynes, JD Dempers, C Wright, WP Fifer, J Angal, TK Boyd, L Burd, E Burger, RD Folkerth, C Groenewald, G Hankins, D Hereld, HJ Hoffman, IA Holm, MM Myers, LL Nelsen, HJ Odendaal, J Petersen, BB Randall, DJ Roberts, F Robinson, P Schubert, MA Sens, LM Sullivan, T Tripp, P Van Eerden, S Wadee, M Willinger, D Zaharie, and KA Dukes. A network of researchers conducted a large-scale study of the outcomes of nearly 12,000 pregnancies among women with high rates of prenatal alcohol use and Sudden Infant Death Syndrome (SIDS) across multiple study sites. Researchers found that infants prenatally exposed to both alcohol and cigarettes beyond the first trimester have a substantially higher risk for SIDS compared to those unexposed, exposed to alcohol or cigarettes alone, or when the mother reported quitting early in pregnancy. These findings further emphasize the role of the early prenatal environment for healthy postnatal outcomes and suggest that screening for substance use early in pregnancy and intervening as soon as possible may help address this public health concern.
“Blockade of IL-17 Signaling Reverses Alcohol-Induced Liver Injury and Excessive Alcohol Drinking in Mice” was published in JCI Insight (2020 Feb 13;5(3). pii: 131277. doi: 10.1172/jci.insight.131277) by J Xu, HY Ma, X Liu, S Rosenthal, J Baglieri, R McCubbin, M Sun, Y Koyama, CG Geoffroy, K Saijo, L Shang, T Nishio, I Maricic, M Kreifeldt, P Kusumanchi, A Roberts, B Zheng, V Kumar, K Zengler, DP Pizzo, M Hosseini, C Contet, CK Glass, S Liangpunsakul, H Tsukamoto, B Gao, M Karin, DA Brenner, GF Koob, and T Kisseleva. Using mouse models, this study demonstrated that the pro-inflammatory cytokine IL-17 is involved in both alcohol-induced liver and brain injury, and in voluntary drinking behavior. The study also found that IL-17 levels are elevated in both humans who drink alcohol excessively and in alcohol-dependent mice. Most significantly, results demonstrated that pharmacological blockade of IL-17 effectively reduces the alcohol-induced liver/brain damage and voluntary drinking in mice, supporting the translational potential of this approach for treatment of alcohol-related pathology.
“Single Cell Transcriptome Profiling of the Human Alcohol-Dependent Brain” was published in Human Molecular Genetics (2020 May 8;29(7):1144-1153. doi: 10.1093/hmg/ddaa038) by E Brenner, GR Tiwari, M Kapoor, Y Liu, A Brock, and RD Mayfield. Investigators applied single-cell RNA sequencing to examine gene expression changes in cells of the prefrontal cortex from postmortem brains of people with AUD and controls. Chronic alcohol exposure altered the expression of multiple genes (coding and non-coding) in all neuronal cell types. The most pronounced expression changes were identified in non-neuronal cells, including astrocytes, oligodendrocytes, and microglia. Each cell type displayed an increase in the expression of genes linked to neuroinflammation, a process associated with excessive alcohol use. This study demonstrates the capacity of single-cell sequencing technology to dissect the complex cell types and gene networks altered in the brains of individuals with AUD.
“Lower Brain Fatty Acid Amide Hydrolase in Treatment-Seeking Patients with Alcohol Use Disorder: A Positron Emission Tomography Study with [C-11]CURB” was published in Neuropsychopharmacology (2020 Jan 7. doi: 10.1038/s41386-020-0606-2) by LM Best, B Williams, B Le Foll, E Mansouri, RP BazinetL Lin, V De Luca, D Lagzdins, P Rusjan, RF Tyndale, AA Wilson, CS Hendershot, M Heilig, S Houle, J Tong, SJ Kish, and I Boileau. Fatty acid amide hydrolase (FAAH), an enzyme that metabolizes the endogenous cannabinoid anandamide, has been implicated in AUD. This study used positron emission tomography with a carbon-11 radiotracer to measure FAAH binding in the brains of individuals with AUD during early and protracted abstinence from alcohol compared to healthy controls. Brain levels of FAAH were lower during early abstinence (3-7 days) in individuals with AUD and were correlated with elevated anandamide levels and a higher number of drinks per week prior to abstinence. FAAH levels appeared to normalize after 2-4 weeks of monitored abstinence. These findings suggest that an endocannabinoid-activating process may be associated with heavy drinking in AUD, implying a unique target for therapeutic intervention in the brain.
“History of Suicidality and Alcohol Craving Trajectories During Inpatient Treatment for Alcohol Use Disorder” was published in Drug and Alcohol Dependence (2020 Apr 1;209:107918. doi: 10.1016/j.drugalcdep.2020.107918) by R Janakiraman, JL Gowin, ME Sloan, ML Schwandt, N Diazgranados, VA Ramchandani, and LE Kwako. To determine whether past suicidality affects the course of AUD, researchers examined whether previous suicidal ideation or attempts are associated with treatment response in individuals with AUD. Participants undergoing detoxification and residential treatment for AUD were assessed for history of suicidal ideation with or without suicide attempts, and alcohol craving was measured weekly during treatment. Individuals with a history of suicide attempts showed higher levels of craving throughout treatment compared to those without a history of suicidality. These results support current guidelines on assessing suicidal ideation in patients with substance use disorders.
“Using Death Certificates to Explore Changes in Alcohol-Related Mortality in the United States, 1999 to 2017” was published in Alcoholism: Clinical and Experimental Research (2020 January 07; 44(1):178-187) by AM White, IP Castle, RW Hingson, and PA Powell. This study revealed that alcohol-related deaths doubled from 1999 to 2017, with death rates highest among men and middle-aged and older adults (ages 45-74). Death rates increased over time across all age groups except 16-20 and 75+; the increase in death rate over time was greater in women than in men. These statistics align with other recent reports that have highlighted changing trends in drinking patterns and increased consequences of alcohol in women and the aging population. Alcohol plays a prominent role in “deaths of despair,” contributing to 15-20 percent of all drug overdoses, 26 percent of suicides, and 50 percent of liver disease deaths.
“Alcoholics Anonymous and Other 12-Step Programs for Alcohol Use Disorder” was published in Cochrane Database of Systematic Reviews (2020 Mar 11;3(3):CD012880. doi: 10.1002/14651858.CD012880.pub2) by J Kelly, K Humphreys, and M Ferri. This systematic review examined outcomes of over 10,000 participants from 27 studies that compared peer-led Alcoholics Anonymous (AA) or professionally delivered Twelve-Step Facilitation (TSF) with other behavioral interventions such as motivational enhancement therapy or cognitive-behavioral therapy, TSF treatment variants, or no treatment. Across a variety of measures, AA performed at least as well as other behavioral treatments for AUD, and AA was more effective in increasing abstinence. These results suggest that AA and TSF can offer a low-cost, effective treatment option for maintaining abstinence among those with AUD.
Discussion:
Scott Russo, Ph.D., asked if there were any collective efforts to centralize post mortem tissues collected from COVID 19 patients, particularly for liver and brain that might be informative for the NIAAA mission. Antonio Noronha, Ph.D., responded that NIH has a central repository of clinical samples and is in the process of opening up repositories with clinical samples around the country; the BRAIN Initiative also has a repository on the West Coast. NIAAA itself does not have a repository. He said he would follow up to learn more about the availability of COVID-19 tissue samples at the brain bank in Australia that NIAAA uses and at the BRAIN Initiative repository. Dr. Koob noted a comment from Dr. Russo that his institution, the Icahn School of Medicine at Mount Sinai, has been aggressively collecting such tissue samples; Dr. Noronha said he would follow up with Dr. Russo. Laura Odell, Ph.D., inquired if the COVID-10 NOSIs are open to immune alcohol questions or if they needed to include COVID itself. Drs. Bautista and Jung confirmed that the NOSIs would cover alcohol immune interactions. Dr. Jung stated that the highest priority for the supplement grants, due to limited funding, are those that include COVID in the study. Alcohol immune issues remain a high priority for the Institute, but researchers should submit such study proposals under the usual funding mechanisms. Regarding administrative supplements for activities disrupted by COVID-19, Dr. Smith inquired if the eligibility for those applying for fellowships will be extended, just as for current fellows. Dr. Bautista responded that NIAAA will have to check for fellowships because that program is mandated by Congress. There should not be a problem with K99 and K01 grantees nor for those in an F32 program because the number of post-doc years does not matter. K99 grantees need to submit a letter requesting an extension of eligibility. Dr. Koob asked about the status of predoctoral and postdoctoral fellows. Dr. Bautista responded that he believes predoctoral fellows will be covered; the critical issue is when the Ph.D. is awarded. There is no limit on postdoctoral applicants regarding when they apply. Edith Sullivan, Ph.D., commented that she really appreciates the NIAAA Treatment Navigator as a point of reference for treatment providers.
Definition of Recovery
Dr. Koob introduced Brett Hagman, Ph.D., Program Director in the Division of Treatment and Recovery Research, who reported on a process that he, Daniel Falk, Ph.D., Program Director in the Division of Medication Development, and Raye Litten, Ph.D., Acting Director, Division of Treatment and Recovery Research and Division of Medication Development, have been undertaking to create a definition of recovery.
NIAAA does not currently have a definition of recovery from AUD. Prior definitions of recovery have limitations: They do not distinguish between alcohol and other drug use; require abstinence from both alcohol and substance use; do not include the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnostic criteria as part of the recovery process (i.e., no focus on remission from AUD); and do not link remission and cessation from heavy drinking in relation to improvements in biopsychosocial functioning and quality of life constructs. Therefore, the field needs a common definition that can be used by diverse stakeholders for increased consistency in recovery measurement and to stimulate research to better operationalize recovery.
Dr. Hagman and his colleagues pursued a multi-step process to define recovery, beginning with a review of the literature on recovery-based processes and trajectories, a review of definitions of recovery; and a review of statistical analyses conducted by an internal NIAAA data team. They then identified and consulted with over 30 key recovery stakeholders in telephone-based qualitative interviews employing an iterative evaluation approach.
The result of this process is the following proposed definition of recovery from AUD: “Recovery is a process through which an individual pursues both remission from AUD and cessation from heavy drinking. An individual may be considered recovered if both remission from AUD and cessation from heavy drinking are achieved and maintained over time. For those experiencing alcohol-related functional impairment and other adverse consequences, recovery is often marked by the fulfillment of basic needs, enhancements in social support and spirituality, and improvements in physical and mental health, quality of life, and other dimensions of well-being. Continued improvement in these domains may, in turn, promote sustained recovery.”
Two key features of this definition include: Remission from DSM-5 AUD: “Remission from alcohol use disorder (AUD), as defined by DSM-5 criteria, requires that the individual not meet any AUD criteria (excluding craving)”; and Cessation from Heavy Drinking: “Cessation from heavy drinking is defined as drinking no more than 14 standard drinks per week or 4 drinks on a single day for men and no more than 7 drinks per week or 3 drinks on a single day for women.” Both are categorized based on duration: initial (up to 3 months), early (3 months to 1 year), sustained (1 to 5 years), and stable (greater than 5 years)
Future directions include publishing the proposed definition in a peer reviewed alcohol journal, with commentaries from several researchers (early fall 2020); development of NIAAA research initiatives to understand recovery utilizing the new definition (fall 2020/on-going); dissemination (e.g., round table discussions with recovery researchers; symposia at research conferences) (fall 2020/on-going); and continued evaluation of the definition, which is open to revision based on empirical evidence (fall 2020/on-going)
Discussion:
Beth Kane-Davidson and Dr. Sullivan supported the importance of the definition and its utility to the field. Jill Becker, Ph.D., asked Dr. Hagman why spirituality was included in the definition. He responded that the goal was to make the definition as inclusive as possible; spirituality originated with AA and is noticeable among those in recovery. As the definition is still in development, it’s possible that spirituality will not be included in the end. Christopher Carpenter, Ph.D., asked Dr. Hagman about how the various recovery definitions align with existing national surveys, such as the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) and the National Survey on Drug Use and Health (NSDUH). Daniel Falk, Ph.D., explained that the basic issue is the inclusion of cessation of heavy drinking, rather than abstinence only. The confluence of evidence is that the AUD consequences are comparable between those with no heavy drinking and those who are abstinent over the long term. Further, the Food and Drug Administration (FDA) now accepts a reduction in the proportion of patients with no heavy drinking days as a satisfactory endpoint in clinical trials. Finally, the 30 stakeholders who provided input during the development process all appeared to accept the cessation of heavy drinking as part of the definition of recovery.
Concept Clearances
NIAAA staff provided information about four proposed concept clearances.
Alcohol and Aging
Dr. Koob introduced András Orosz, Ph.D., Program Director, Division of Metabolism and Health Effects, to present a concept clearance on alcohol and the aging process, a priority topic in the NIAAA Strategic Plan. Dr. Orosz began by noting that people over 65 years constitute the fastest growing segment of the U.S. population with increasing alcohol consumption, particularly among women. Diagnosing AUDs in this population is more difficult as symptoms may be masked by aging. This silent epidemic represents a significant public health problem as aging is one of the biggest risk factors of chronic, non-communicable diseases that are exacerbated by alcohol.
The purpose of the proposed initiative is to improve understanding of the effects of alcohol consumption on aging across different levels of biological organizations including the molecular, cellular, tissue, organ, organism, and societal domains. The following broad research areas are targeted: 1) Basic and clinical research defining the effects of alcohol consumption on lifespan, health span and age-related diseases depending on volume, drinking pattern and duration of drinking; 2) Research to inform evidence-based guidance for diagnosis, prevention and treatment of alcohol use disorders in older drinkers; and 3) Research to extend health span of older drinkers and decrease the health care burden of age-related diseases.
Examples of research objectives addressing basic biological mechanisms, metabolism and health effects include (but are not limited to) identifying the effect of alcohol on pillars of aging, including macromolecular damage, epigenetics, inflammation, adaptation to stress, protein homeostasis (proteostasis), cellular senescence, stem cell regeneration, and metabolism; infectious and noninfectious diseases and frailty in older adults; sex as a biological variable on the alcohol-aging axis; aging biomarkers, such as senescence, telomere attrition, and the “epigenetic clock.” Examples of neuroscience include establishing the effect of alcohol on neurobiological mechanisms contributing to healthy and pathologic brain aging; neuroimmune interactions and neuroinflammation in aging; and prenatal or adolescent alcohol exposure in aging and aging pathologies. Examples related to epidemiology, prevention, and treatment include development of screening vehicles, prevention, behavioral and drug therapies targeted for older adults; identification of vulnerabilities of high-risk groups among older adults including older adults with comorbidities, women, racial, ethnic, socioeconomic, immigrant, sexual and gender minority status; and enhancing understanding of polypharmacy-alcohol interactions in older adults with emphasis on emerging legal and illicit drugs.
The proposed approach for implementing this concept includes publication of a NOSI (no set-aside NIAAA funds) and collaboration with NIA. NIA Alzheimer’s disease supplements may be utilized to collect preliminary data for the initiation of these studies. The anticipated outcomes of the initiative are improved understanding of alcohol’s effects on aging and age-related diseases, as well as evidence-based guidance for diagnosis, prevention and treatment for alcohol use disorders in older drinkers.
Discussion:
Dr. Smith inquired about the potential review process for this initiative to assure that reviews are conducted from an integrated, cross-disciplinary perspective. Dr. Bautista responded that review issues will be addressed in the final draft of the NOFO. Dr. Koob asked Dr. Orosz about the types of applications that have come in thus far and if there have been any review problems. Dr. Orosz responded that applications were sent to a regular study section that had reviewers with expertise in aging research. Depending on the applications received, those with similar foci can be grouped together so that review panels with specific expertise can be put into place. Dr. Sullivan called attention to two issues in the investigation of the role of AUD in age-related dementias: the practice of excluding study participants who’ve had an AUD from dementia trials and the failure to pursue current or remote history of AUD in dementia programs. These issues pose roadblocks for identifying and recruiting those with dementia and AUD in research studies. She asked for suggestions on how to address this “head in the sand” problem, which is not uncommon in dementia clinics. Dr. Orosz suggested that NIAAA discuss the issue with NIA; Dr. Jung concurred.
Fetal Alcohol Spectrum Disorders (FASD):
Prevention and Intervention Dr. Koob introduced Bill Dunty, Ph.D., NIAAA FASD Research Coordinator and Program Officer in the Division of Metabolism and Health Effects, who presented a concept clearance on behalf of the NIAAA FASD working group. Prenatal alcohol exposure is a leading preventable cause of birth defects and neurodevelopmental deficits in the United States. Individuals with FASD experience a unique combination of day-to-day challenges, which may include physical, behavioral, cognitive, educational, mental health, and social problems. These may include difficulties in learning and memory, self-control, mood and behavior, attention and organization, communication and language, and daily living and social skills. FASD symptoms appear in childhood and last a lifetime. Although FASD is completely preventable, approximately 11.5 percent of pregnant women still report drinking alcohol in the past 30 days.
The purpose of this concept is to support research that advances prevention approaches to reduce prenatal alcohol exposure and the incidence of FASD, and to develop interventions for individuals with FASD. An analysis of NIAAA’s FASD FY2015-2020 portfolio revealed that prevention (3.4 percent) and intervention (16.1 percent) research comprised approximately one-fifth of the Institute’s total number of new FASD awards during that time.
Therefore, NIAAA seeks to encourage novel prevention and intervention research for FASD across the lifespan. Examples of prevention-related research objectives include, but are not limited to: Design and evaluate novel prevention approaches and improve established methods to prevent prenatal alcohol exposure, especially in high risk and vulnerable populations; implement biopsychosocial, community-based, and policy approaches for preventing prenatal alcohol exposure; and reduce stigma associated with FASD for both biological mothers and affected individuals. Examples of intervention-related research objectives include: Develop and evaluate novel prenatal and postnatal therapeutic approaches, medications, and dietary supplements; pursue interventions to lessen the physical, cognitive, and behavioral deficits and improve health and quality of life for individuals with FASD and their families; and improve implementation and access to evidence-based interventions for individuals with FASD.
Discussion:
Dr. Becker recommended that research funded under this initiative should address sex as a biological variable (SABV). Dr. Dunty acknowledged the importance of SABV. Dr. Smith inquired if the inclusion of dietary supplements in the exemplar research objectives is intended to support the Office of Dietary Supplements and if there is hope the Office will commit funding to the program. Dr. Dunty responded the term “dietary supplements” was included to reflect how choline and other supplements are classified; however, NIAAA would be willing to use her suggested term, “dietary components.”
Epidemiology and Prevention in Alcohol Research
Dr. Koob introduced Michael Hilton, Ph.D., Deputy Director, Division of Epidemiology and Prevention Research, who presented a concept for a NOSI to support epidemiology and prevention in alcohol research. The purpose of this concept is to replace PA-18-390/391/413 that expired on May 9, 2020. This Program Announcement generated 150 applications and 14 funded projected. It was preceded by earlier announcements with the same title, beginning in 2007. The proposed Notice of Special Interest (NOSI) differs from previous Program Announcement (PA) by focusing less on a specific high priority area and more on communicating the broad scope of research topics of interest to NIAAA in the areas of epidemiology and prevention.
Examples of research objectives under this concept include (but are not limited to): Build a better understanding of alcohol misuse among women and identify and evaluate effective strategies to reduce alcohol misuse among females across the lifespan, with particular emphasis on adolescent girls, pregnant women, and breastfeeding women; examine the impact of simultaneous alcohol and drug use on unintentional and intentional injuries and how to prevent simultaneous use; identify the factors driving high-intensity drinking and evaluate strategies to reduce its prevalence; understand the nature and extent of harms that misuse of alcohol imposes on others and evaluate interventions to prevent or reduce such harms; and study the effect of public policy on alcohol use, other substance use, and alcohol related harms.
Discussion:
Laura Nagy, Ph.D., suggested adding COVID-19 interactions with alcohol to the list of research objectives; Dr. Hilton agreed it would be an appropriate addition. Ms. Kane-Davidson expressed support for collecting data about COVID-19 and isolated-related drinking rates. Dr. Carpenter indicated that he strongly supported the DEPR concept. Daniel Calac, M.D., raised a concern about the inclusion of rural communities; they are often undercounted. Drs. Koob and Hilton confirmed that rural communities and underserved populations are addressed in the proposed language of the NOSI.
Alcohol Research Resource Awards (R24)
Dr. Koob introduced Kathy Jung, Ph.D., Director of the Division of Metabolism and Health Effects (DMHE), who presented a concept for the reissue of a funding opportunity announcement on Alcohol Research Resource (R24) Awards. Resource-Related Research Projects are designed to provide materials and services to support and advance biomedical research on a national basis. A resource is a non-hypothesis-driven activity that provides data, materials, tools, or services that are essential to making timely, high quality, and cost-efficient progress in support of alcohol research.
The purpose of this program announcement is to support provision of resources serving biomedical research on AUD and its medical consequences at a national level. Its scope encompasses resources to provide data, materials, tools, or services that are essential to making timely, high quality, and cost-efficient progress in a field. The resource is to be made available to any qualified investigator, should be quality controlled, and not duplicate resources available commercially or through other sources. Resources should be designed to provide service to the broad alcohol research community and should not be limited by regional or institutional focus.
To qualify for funding, the proposed resource must address scientific needs for novel and distinct research capabilities that benefit the wider scientific community; be demonstratively cost effective and deliver distinct and impactful materials or services relative to alternatives; and not otherwise be available to the broader research community. Limited developmental scaling and refinement effort is permissible, but hypothesis-driven aims are not appropriate for this announcement.
Dr. Jung commented that NIAAA seeks to advance research that is timely and of high impact. The Institute does not anticipate increasing the number of Centers and has no plans to sunset any R24s; however, existing grantees must demonstrate that they’re moving the field forward and meeting an unmet need. The metric for success is not publications, but the number of specimens requested and supplied to investigators outside the Center. Applicants should emphasize the number of requests and level of success from the research community, as well as the impact on advancing the field.
Discussion:
Robert Hitzemann, Ph.D., noted that the coronavirus pandemic has negatively impacted many animal studies; he asked how that aligns with the proposed concept. Dr. Jung responded that here have been allowances to let hard-to-find strains be maintained without actual ongoing research. Dr. Koob added that NIAAA will offer support to those labs that need to rebuild through supplements.
General Discussion
Deidra Roach, M.D., reported that NIAAA is a sponsor of the National Academy of Sciences Forum on Mental Health and Substance Use Disorders that will focus on essential components of care for mental health and substance use disorders in primary care settings. Dr. Odell asked for additional discussion about the way COVID-19 is disproportionately affecting different demographic groups. Dr. Koob responded that NIAAA is part of several cross-NIH initiatives addressing the impact of the virus on different groups, as well as an initiative to scale up testing. Patricia Powell, Ph.D., noted that the impact of COVID-19 on minorities and other groups is a high priority within both NIH and NIAAA, but all current plans are not yet publicly available. Bridget Williams-Simmons added that NIAAA is participating in the National Institute on Minority Health and Health Disparities (NIMHD) NOSI competitive administrative supplements on the impact of the COVID 19 outbreak on minority health and health disparities. Vijay Shah, M.D., inquired about the possible long-term impact of COVID-19 on the overall NIH budget and funding for other priority topics. Dr. Koob responded that NIH Director Francis Collins, M.D., Ph.D., has testified to Congress about NIH’s funding needs in light of COVID-19. Ms. Kane-Davidson noted the challenges in providing substance use treatment virtually, which lacks the personal connection that is needed for engagement and retention of patients. Constance Horgan, Ph.D., noted that health services research is a cross-cutting approach that could be integrated into each of the concepts presented today to enhance them.
Consideration of Council February 6, 2020 Minutes/Future Meeting Dates
Council members voted unanimously to approve the minutes of the NIAAA Advisory Council meeting held on February 6, 2020.
Dr. Bautista announced upcoming meeting dates for 2020-2024. In 2020, the Council will meet on May 12, and September 10; the CRAN Council will meet in 2020 on May 13. In 2021, the Council will meet on February 4, May 11, and September 9; the CRAN Council will meet on May 12, 2021. In 2022, Council will meet on February 10, May 10 and September 8; the CRAN meeting will be on May 11. In 2023, Council will meet on February 9, May 9, and September 7; the CRAN Council will meet on May 10. In 2024, Council will meet on February 8, May 14, and September 12; the CRAN Council meeting will meet on May 15.
Adjournment
Dr. Koob adjourned the meeting at 3:41 p.m.
CERTIFICATION
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
/S/
George F. Koob, Ph.D.
Director
National Institute on Alcohol Abuse and Alcoholism
and
Chairperson
National Advisory Council on Alcohol Abuse and Alcoholism
/S/
Abraham P. Bautista, Ph.D.
Director
Office of Extramural Activities
and
Executive Secretary
National Advisory Council on Alcohol Abuse and Alcoholism