DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
140th Meeting of the
NATIONAL ADVISORY COUNCIL ON ALCOHOL ABUSE AND ALCOHOLISM
September 17, 2015
The National Advisory Council on Alcohol Abuse and Alcoholism (NIAAA) convened for its 140th meeting at 9:00 a.m. on Thursday, September 17, 2015, at NIAAA headquarters in Rockville, Maryland. The Council met in closed session to review grant applications; the meeting recessed at 9:55 a.m. 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. Dr. George Koob reconvened the Council in open session at 10:16 a.m.
Council Members Present:
Carol A. Casey, Ph.D.
Linda L. Chezem, J.D.
Carlo C. DiClemente, Ph.D.
Paul J. Gruenewald, Ph.D.
Paul J. Kenny, Ph.D.
Sarah N. Mattson-Weller, Ph.D.
Craig J. McClain, M.D.
Robert O. Messing, M.D.
Patricia E. Molina, M.D., Ph.D.
Adolf Pfefferbaum, M.D.
Rajita Sinha, Ph.D.
Dan Kivlahan, Ph.D., ex officio
NIAAA Director and Chair: George F. Koob, Ph.D.
NIAAA Deputy Director: Kenneth R. Warren, Ph.D.
Executive Secretary: Abraham P. Bautista, Ph.D.
Vicki Buckley, M.B.A.; Vivian Faden, Ph.D.; Ralph Hingson, Sc.D., M.P.H.; Robert Huebner, Ph.D.; M. Katherine Jung, Ph.D.; Gary Murray, Ph.D.; Antonio Noronha, Ph.D.; Patricia Powell, Ph.D.
Other Attendees at the Open Session:
Approximately 45 observers attended the open session, including representatives from constituency groups, liaison organizations, NIAAA staff, and members of the general public.
Call to Order and Introductions
Dr. George Koob called the open session of the Council meeting to order at 10:16 a.m. on Thursday, September 17, 2015. He opened the meeting by thanking the four retiring members of the Council—Judge Linda Chezem, Dr. Fulton Crews, Ms. Marianne Fleury, and Dr. Craig McLain-- for their service. Council members and senior NIAAA staff introduced themselves.
Dr. Koob highlighted key recent Institute activities, referring to the written Director’s Report.
NIAAA budget. The current fiscal year (FY) ends September 30, 2015. The 2016 appropriations bill is pending in Congress. NIH expects to begin the new fiscal year under a continuing resolution that will maintain the current funding level of $30.3 billion; the President has asked Congress for $1 billion more. If approved, NIAAA’s funding would go up from $447.2 million to $459.8 million. In FY 2015, NIAAA funded 676 applications, down slightly from the 686 Research Project Grants (RPGs) funded in 2014. There were also 152 competing awards funded this year. Work has begun on the FY 2017 budget, which the President presents to Congress in February 2016.
Legislative initiatives. The 21st Century Cures Initiative, led by Representative Fred Upton, Chairman of the House Energy and Commerce Committee, seeks to enhance and accelerate the discovery, development, and delivery of new treatments and cures. If adopted, it would provide $1.86 billion each year from FY 2016 – 2020 for an NIH Innovation Fund, as well as an increase in the loan repayment limit for emerging scientists. The bill passed the House of Representatives on July 20, 2015. The Senate version is expected this fall, but it’s not clear if it will resemble the original bill.
NIAAA staff transitions. Dr. Koob noted a number of staff changes at NIAAA. Departures include: Mr. Keith Lamirande has taken a position as the executive officer for the National Center for Advancing Translational Sciences (NCATS); Ms. Charlene Patrick has moved to NICHD as lead administrative officer; Ms. Fanny Rio Spears has joined the Texas Heart Institute; and Ms. Tamica Wilkerson has become an administrative officer at NCATS. Ms. Vicki Buckley will serve as NIAAA’s acting executive officer while a national search is undertaken to fill the position vacated by Mr. Lamirande.
Honors and awards. Dr. Koob announced several awards bestowed on NIAAA staff members. Dr. David Goldman received the Research Society on Alcoholism (RSA) Distinguished Researcher Award and the RSA Seventh Annual Ting-Kai Li, M.D. Plenary Lecture Award. The following NIAAA intramural fellows were awarded the NIH Fellow Award for Research Excellence: Dr. Resat Cinar; Dr. Joshua Gowin; Dr. Lindsay Halladay; Mr. Yong He; Dr. Teresa Ramirez; Dr. Ming-Jiang Xu; Dr. Jia Yan; and Dr. Zhou Zhou.
New funding opportunities. NIAAA has issued three new Funding Opportunity Announcements (FOAs): Consortia for HIV/AIDS and Alcohol-Related Research Trials (CHAART) Project; Screening and Brief Alcohol Interventions in Underage and Young Adult Populations; and Alcohol Use Disorder: Behavioral Treatment, Services and Recovery Research. As the NIAAA strategic plan gets put into place, there will be new FOAs. Currently, the focus is on the strategic planning itself. NIAAA is also participating in new FOAs, including the NIH BRAIN Initiative; NIH Big Data to Knowledge (DB2K) initiative; HIV in sexual and gender minority populations; translational research in collaboration with the NIH Clinical Center; and supplements to support workforce diversity.
NIAAA research highlights. Dr. Koob highlighted the findings of several new journal articles based on research funded by NIAAA and their implications for the field. “MIR-125B Protects Against Ethanol Induced Apoptosis in Neural Crest Cells and Mouse Embryos,” published in Experimental Neurology, suggests that a miR-125b-based intervention could diminish the harm caused by prenatal alcohol exposure (PAE). (Chen X et al. Exp Neurol, 2015 May 27;271:104-111. doi:0.1016/ j.expneurol. 2015.04.026).
“Effect of Roux-en-Y Gastric Bypass Surgery: Converting 2 Alcoholic Drinks to 4,” published in JAMA Surgery, found that women who had had the surgery reached the same alcohol blood concentration in half the number of drinks, underscoring the need for patient education in alcohol metabolism that occur after RYGB. (Pepino MY et al. JAMA Surg. 2015 Aug 5. doi: 10.1001/jamasurg.2015.1884) .
“Brain Development in Heavy-Drinking Adolescents,” published in the American Journal of Psychiatry, provides further evidence that heavy drinking during adolescence alters the trajectory of brain development; this study was highlighted at the NIAAA program at the American Psychological Association.((Squeglia LM, Tapert SF, Sullivan EV, Jacobus J, Meloy MJ, Rolfing T, Pfefferbaum A. Am J Psychiatry, 2015, 172(6):532-42).
“Effects of Varenicline on Neural Correlate of Alcohol Salience in Heavy Drinkers” in the International Journal of Neuropsychopharmacology demonstrated the effects of varenicline on activation of brain regions associated with motivation and incentive salience for alcohol reward, helping to explain its effectiveness in reducing alcohol consumption. (Vatsalya V et al. Int J Neuropsychopharmacol. 2015 doi: 10.1093/ijnp/pyv068).
“Role of the Alpha1 Blocker Doxazosin in Alcoholism: A Proof-of-Concept Randomized Controlled Trial,” published in Addiction Biology, found that the alpha 1 blocker doxazosin reduced alcohol drinking and craving in alcoholic patients with high density family history of alcoholism, but not in those with a low family history, suggesting that doxazosin may be effective selectively in alcoholic patients with a significant family history of alcoholism. (Kenna GA et al. Addict Biol. 2015 Jun 2).
“Alcohol Use Predicts Sexual-Decision-Making: A Systematic Review and Meta-Analysis of the Experimental Literature” in AIDS Behavior found alcohol use contributed to a greater desire to engage in unprotected sex so that addressing alcohol in sexual risk-taking interventions should increase their effectiveness and reduce potential adverse consequences, including HIV. (Scott-Sheldon et al., AIDS Behav. 2015 Jun 17).
“Cannabinoid Receptor 1 Promotes Hepatocellular Carcinoma Initiation and Progression Through Multiple Mechanisms” in Hepatology found that genetic deletion of CB1R suppresses the growth of hepatocellular carcinoma (HCC) through specific mechanisms, thus underscoring the therapeutic potential of peripheral CB1R blockade in HCC. Bani Mukhopadhyay, Ph.D., a Fellow in the NIAAA Laboratory in Physiologic Studies, was lead author. (Mukhopadhyay B et al. Hepatology, 2015 May;61(5):1615-26.doi:10.001/hep.27686. Epub 2015 Feb17).
NIAAA will launch CollegeAIM on September 22 at the National Press Club. Dr. Koob reported that he has spoken about it to the news media, and NIAAA is reaching out to all colleges and universities across the country. CollegeAIM is a new resource to help schools address harmful and underage student drinking by providing a matrix of individual and environmental-level interventions that includes the cost, effectiveness, and level of research supporting the effectiveness of each intervention. Dr. Vivian Faden spearheaded its development, working with a panel of 16 expert reviewers. The goal is to have young people understand that not everyone is drinking as much as they may think they are, plus the danger of alcohol intake at their stage in life. While there is an overall decrease in the percentage of young people who are drinking, there is a dramatic increase in the intensity of their drinking. Instead of 3-4 drinks people are consuming 10-15 drinks at a time; this is highly dangerous. The challenge now is to determine if the new tool makes an impact. Dr. Koob suggested that this approach could be a model for how NIAAA translates evidence-based information of alcohol use in other areas.
Discussion: Dr. Faden noted that NIAAA is launching CollegeAIM now because colleges are focused on alcohol consumption as students go back to school. Developing the tool involved trying to build consensus in a field with many controversies. There were six developers, an environmental group led by Dr. Traci Toomey (University of Minnesota) and an individual group led by Dr. Mary Larimer (University of Washington). Almost 60 interventions were coded across 11 parameters. CollegeAIM is a practitioner’s guide, designed to help colleges choose interventions wisely, particularly in a resource-constrained environment. NIAAA has also established a website with more information than the print version provides. Users can click on any intervention, then click on references to go directly to the research articles supporting the intervention. Dr. Patricia Molina observed that there is a lack of understanding about what works and where to turn for guidance at colleges and universities; it will be critical to publicize the new tool well. Dr. Koob emphasized that he wants NIAAA to be the evidence-based source of information about alcohol for the country. He challenged Council members to identify areas where NIAAA can translate something it has learned into useful tools for people to use.
Concept Council Clearance
Dr. Kendall Bryant, Director of Alcohol and HIV/AIDS Research at NIAAA, presented information about a new change in direction in HIV/AIDS, HCV, and alcohol-related research across NIH. Over 1 million people live with HIV in the United States; there are 50,000 new infections each year. People can live long lives with AIDs; yet HIV/AIDS remains a challenging epidemic. Less than 50% of those in the U.S. with HIV/AIDS have control of their viral loads. Now is not the time to pull back but to capitalize on new advances in research. The goal is zero (0) new infections and zero (0) new deaths from AIDS. It is critical that NIH pursue research in clinical, behavioral and social science research, including the testing of interventions. The purpose of Dr. Bryant’s presentation is to elicit ideas from Council on how NIH should approach doing so.
In the planned approach, NIH will use cooperative agreement mechanisms (i.e., U01, U10, U19, U54, U56, U19, U10 and UM1), to allow for collaboration between investigators and institutions that have existing infrastructure and resource centers to identify and measure the impact of research related to the reduction of new infections, increases in effectiveness of treatment for individuals over their lifespan, or advancing a functional cure. This cooperative approach will help build a “Team Science” framework to carry out research of high priority to NIAAA, NIH, and national plans. This includes the White House National HIV/AIDS Strategic Plan 2020, which seeks to identify 90% of newly infected individuals and engage 90% of them in care. The National Strategy’s collaboration goals include establishing cross-agency partnerships within the Federal government; formulating recommendations for the HIV Care Continuum Initiative, and developing and implementing a core set of HIV program indicators (e.g., a standardized definition of alcohol use) to support data sharing and increased transparency.
Because of the increasingly constrained budget, NIH began to reassess its research portfolio and focus its scarce resources on the highest priorities in the field. In May 2014, the Office of AIDS Research Advisory Council (OARAC)’s HIV/AID Research Portfolio Working Group released a report identifying priorities for NIH in core areas of HIV/AIDS research for the next three to five years. The FY 2015 Trans-NIH Plan for HIV-Related Research followed, reflecting input from the scientific and academic communities, as well as community constituency groups. A special group of Institute and Center (IC) extramural and intramural leadership was convened under the direction of Dr. Lawrence Tabak. Most recently, on August 12, 2015, the NIH Office of AIDS Research released NOT-OD-15-137 that identified high, medium, and low-priority topics of research and set guidelines for using AIDS-designated funds.
The high priority research areas address reducing incidence, including the development of vaccines; the next generation of HIV therapies with better safety and ease of use over the life span; research toward a cure for HIV/AIDS; and HIV-associated comorbidities and co-infections. The direct study of multiple co-infections, co-morbidities, and complications in the context of HIV infection, disease, and treatment will expand understanding of root causes and expressions of disease that will benefit areas of NIH investigation beyond HIV/AIDS. The key question for NIH in addressing these co-infections and co-morbidities is the appropriate allocation of dedicated AIDS funds (as compared to non-AIDS funds) to studies that address them. There are also cross-cutting areas to consider, such as basic behavioral and biological research, health disparities in key populations, and cross training in areas such as HIV and alcohol use. An example of a co-infection/co-morbidity issue is liver disease. Progression to advanced liver disease remains a leading cause of death among HIV-infected persons. The Veterans Aging Cohort Study (VACS) was the largest study to date of HIV-infected individuals. It showed that among those patients with hepatitis C, there was a linear increase in mortality among those infected with HIV relative to their level of alcohol use, compared to those without HIV. It demonstrated that medicine could have a dramatic impact on the mortality of those with HIV by providing treatment of hepatitis C and simultaneously addressing alcohol use.
Dr. Bryant presented questions for Council about the new approach that included increased competitiveness for funding; what is specific to NIAAA; the interaction with other NIAAA collaborative initiatives; application to existing research; the solicitation of new research proposals; eligibility for participation; and the impact on new announcements and portfolio composition. Key points reviewed by Dr. Bryant addressed the use of cooperative agreement mechanisms to allow for collaboration between investigators and institutions that have existing infrastructure and resource center to identify and measure the impact of research that reflects the priorities described above. He pointed out that this is not specific to NIAAA resources, but could involve collaboration with Centers for AIDS Research (CFARs) and other ICs for the use of existing HIV+ or at-risk cohorts with detailed clinical information. NIAAA already collaborates with NICHD in a U19 agreement. The collaboration fits in with other NIAAA HIV collaborative and consortium programs that address developing and testing new interventions to improve the HIV Care Continuum (e.g., developing digital/mobile health technology) and measuring the impact of comorbidities on HIV outcomes (e.g., HCV, HBV, TB). The initiative applies to both existing NIAAA-funded research proposals, as well as to the solicitation of new research proposals. There will be no restrictions on eligibility for participating in the collaboration; this approach should open up alcohol expertise to the HIV community. For FY2017, NIAAA anticipates that there will be no effect on the use of other cooperative agreement mechanisms. OAR is putting into place a new review process for all Program Announcements (PAs) and Requests for Applications (RFAs) that are planned for release by an IC.
Discussion: Dr. Koob noted that there will be much more scrutiny on the HIV portfolio to address the stated goals and priorities as NIH strives to be responsive to constituency groups. Dr. Carlo DiClemente stated that SAMHSA is encouraging people to get screened for mental health, substance abuse disorders, and HIV. He asked if there was a way to tie research findings into other agencies’ translational initiatives, such as HRSA’s Ryan White Act. Dr. Bryant responded that NIAAA has been working on implementation research, but its role in implementing effective interventions is as an active partner to others. Dr. DiClemente stated that he was thinking of the Clinical Trials Network (CTN), putting the community together with research. Dr. Bryant noted that vertical integration around the highest-risk populations was a goal of the initiative. For example, finding ways to develop treatments for comorbidity of alcohol and hepatitis C by finding places with high HIV rates and then engage people in care. Judge Chezem and Dr. McClain confirmed there were high rates of alcohol use and hepatitis C among people with AIDS in rural communities. Dr. Bryant noted that a team science approach is needed to addressing these issues. He asked Dr. McClain if he had anything to report from the Council of Councils. Dr. McClain stated that there will be redistribution of funds; those who will lose research dollars are those who are not studying patients with HIV or basic science projects with a low HIV tie-in. Dr. Rajita Sinha inquired if there will be more scrutiny of current projects or just future applications. Dr. Bryant responded that current grantees will be grandfathered in, but will need to refocus on high priority areas when they come up for renewal. Dr. Sinha suggested informing current grantees about this, so that they can collect needed data; Dr. Bryant explained that review processes were also changing and it may be premature to share anything yet. Dr. Koob concluded the discussion by emphasizing the NIAAA is trying to make it clear that alcohol has a role in the pathophysiology of this epidemic.
Update on the Common Rule
Dr. Troy Zarcone, Health Science Administrator in the NIAAA Office of Science Policy and Communication, described the current Notice of Proposed Rulemaking (NPRM) posted in the Federal Register with a request for comments about changes to the Common Rule. The Common Rule is the Federal Policy for the Protection of Human Subjects, originally issued in 1991, that requires basic protections for human subjects involved in biomedical and behavioral research in the United States. The rules outline the basic provisions for Institutional Review Boards (IRBs), informed consent, and Assurance of Compliance; they also establish additional protections for special populations, such as pregnant women, children, and incarcerated individuals. The U.S. Department of Health and Human Services (HHS) and other Federal agencies are proposing to modernize the Common Rule based on changes in the social, cultural, and technological environment, e.g., privacy concerns related to the Internet and advances in genetics. Additional goals of the proposed changes are to reduce the burden on investigators and improve the public trust in human-subjects research. About half of NIAAA’s portfolio involves human subjects. NIAAA Council members are asked to review the NPRM and comment on how the proposed changes will affect NIAAA’s human-subject research.
The NPRM proposes extending the scope of the policy, i.e., it proposes that the Common Rule be applied to all clinical trials, regardless of funding source, conducted at a U.S. institution receiving federal funds for non-exempt human-subjects research. The NPRM also addresses informed consent, promoting shorter consent forms highlighting key information that includes details a reasonable person would want to know in making a decision to participate. Consent forms for clinical trials would require a one-time posting for public review. Consent would be required for secondary research with a biospecimen and a “broad” consent form could allow a person to give permission to use his or her biospecimen for future unspecified research. Reducing the burden on investigators would be accomplished by defining some activities as non-research, expanding categories of exempt research, changing conditions and requirements for waiving consent, allowing a single IRB of record for multi-site studies, and eliminating continuing review for certain studies, e.g., those undergoing expedited review or involving data analysis only.
NIH encourages comments from the public, patient organizations, industry, investigators and research institutions as part of the stakeholder engagement process. All comments must be submitted by December 7, 2015.
Discussion: Dr. DiClemente inquired if NIH was reaching out to current university IRBs for comment. Dr. Zarcone replied that NIH could not engage the public until the proposed rules were published in the Federal Register so that everyone has an equal opportunity to respond. Judge Chezem noted that the IRB at her university was planning to comment. Dr. Zarcone stated that everyone can submit statements as an individual, NIAAA employees may comment as private citizens (not using their NIAAA affiliation, title or government email address). Dr. Sinha asked who will categorize research risk and whether there are efforts to separate clinical trials from other human subject research. In response, Dr. Zarcone recommended that Council members read the specific language in the NPRM to determine if the issues are addressed appropriately.
Dr. Sarah Mattson-Weller raised concerns about the amount of NIH funding and support for research on prenatal alcohol exposure, especially clinical research. The most recent estimate of the prevalence of fetal alcohol exposure (FAE) is 1 to 2.5% of the population. A review of recent R01 submissions indicated that there were 19 R01s related to prenatal alcohol exposure, including both clinical and pre-clinical studies; 10% received a score less than 10% and 58% were unscored. In the clinical domain, in particular, there were five applications and 80% were not scored. The fifth one received a low (unfavorable) score. Most clinical fetal alcohol studies are reviewed by one study section, which does not appear hospitable to prenatal alcohol studies. According to RePORTER, there are 15 active R01 grants on FAE but only three are for clinical research and only two of those are active. In contrast, there are 140 autism grants and 199 on ADHD, conditions that also affect children. Her concern is that clinical research applications are not receiving the attention they deserve because the study section reviewers are not representative of the clinical research field and there is a dwindling number of senior investigators available to mentor junior researchers and provide the necessary knowledge to critically review grant applications.
Due to this lack of funding and senior-level mentoring available to the field, junior investigators are leaving to go to research areas that are better funded. Prenatal alcohol exposure is a critically important public health concern but the field is becoming effectively extinct due to attrition. She requested a comparison of the success rate of fetal alcohol exposure applications, compared to those for autism and ADHD.
Discussion. Dr. Koob responded that it is unfair to compare the NIAAA budget to that of NICHD. NIAAA has allocated 10% of its budget on FAE for quite some time. However, a large proportion of the budget for FAE is earmarked for U mechanisms with other ICs, limiting the amount available for R01s. Concerns with study sections may be well placed, since there have been problems in other study sections over time. Dr. Mattson-Weller replied that the problem is not NIAAA’s lack of support for FAE research, but that the level of importance is not being passed on to the people who are reviewing the applications. Dr. Kenneth Warren noted that U funding is reviewed by NIAAA where there is subject matter expertise, rather than the Center for Scientific Review (CSR). He monitors applications going to CSR study sections and has noted over the years the limited number of individuals who are active investigators in the FAE field serving on those sections. The clinical research applications go to a basic research study section. Currently, there is no one on that group with alcohol expertise. There is a need for senior people from the FAS/FAE community to be on the CSR committees. NIAAA can communicate that, but the final decision rests with CSR. He recommended that NIAAA communicate with CSR director Dr. Richard Nakamura about this; it would be extremely useful to have the names of senior people in the field to recommend as reviewers. Dr. Koob responded that this is a more generic issue than just FAS/FAE and applies to other alcohol-related research applications. Dr. Bautista stated that Dr. Nakamura sends NIAAA the list of reviewers and the Institute can make recommendations for the incoming roster. He recommended encouraging the FAS community to review at CSR. Dr. Sinha supported the idea of making the issue more general. She noted that alcohol-related grant applications have not done well in the imaging study section. Dr. Koob stated NIAAA would follow up with CSR and asked Council members to send their comments to Dr. Bautista so he could follow-up with Dr. Nakamura.
Consideration of Minutes of the June 2015 Council Meeting and Future Meeting Dates
Council members unanimously approved the minutes of the NIAAA Council meeting held June 10, 2015.
NIAAA has scheduled its next Council meeting for February 11-12, 2016. In 2016 the Joint NIAAA, NCI, and NIDA (CRAN) Council meeting will take place on February 11, and the NIAAA Council will meet on February 11–12, June 9, and September 15. In 2017 the NIAAA Council will meet on February 9, May 2, and September 14. The CRAN Council meeting will take place on May 3, 2017. In 2018 the Council will meet on February 8, May 15, and September 13; the CRAN Council will meet on May 16, 2018.
Challenges of the Justice system in the Prevention and Treatment of Alcohol Abuse
Judge Linda Chezem presented information about the role of alcohol research as it intersects the criminal justice system. An estimated 6,899,000 persons were incarcerated at the end of 2013, with an additional 4,851,400 under community supervision. Their reportable offenses are varied, but many are likely attributable to alcohol use disorder (AUD). In general, criminal justice data is incomplete and needed data about alcohol and drug-related crime is not collected. Much of the known data about alcohol’s role in criminal justice comes from studies published in the 1990s and early 2000s; a review of the issue titled “The Scope of Alcohol Problems in the Criminal Justice System” by Sandra Lapham published in 2004/2005 remains one of the best sources for data on the topic. The incredible complexity of the justice system with 50 state systems and multiple Federal systems contributes to difficulties in collecting and reporting timely, uniform data.
The newest approach to improving the justice system is Justice Reinvestment, a data-driven approach to improve public safety, reduce corrections and related criminal justice spending, and reinvest savings in strategies that can decrease crime and reduce recidivism. In place since 2006, it is co-sponsored by the Department of Justice and foundations, including the Pew Charitable Trusts, Annie E. Casey Foundation, and the McArthur Foundation. In the past two years, funding for the BJA Justice Reinvestment Initiative has increased; however, funders want data and evidence that funded programs are effective. Justice Reinvestment can work if there is good data collection, with strong evaluations, an informed research agenda, adequate funding for both programs and research, and knowledgeable and creative researchers. NIAAA is in a position to help. The evidence about which programs are effective should be coming from the alcohol research community. There is also a good argument for funding from both the justice and research communities. Justice Reinvestment will fail if there is no evidence base.
Community-level prevention and treatment programs are unaware that research on screening, prevention, and control of alcohol exists, and probation and parole programs lag even further behind the health-based systems. The knowledge-to-practice pipeline is broken for a variety of reasons; as a result, Indiana just passed a law that provided $50 million for programs that don’t exist. Another problem is that defendants are ordered to pay their own treatment fees; unpaid fees are turned over to collection agencies in some states. Consequently, people are not able to regain standing in the community; their records, even for minor offenses, cannot be expunged and disqualify them for jobs and credit. They are under extreme pressure to meet the demands of treatment, pay user’s fees, and simultaneously keep a job.
The public may lose faith in alcohol prevention and treatment and view the research as flawed, if effective treatment programs tailored to meet individual needs are not available and offenders reoffend. Additional challenges include recognizing that prenatal exposure to alcohol is a major issue in providing equal access to justice; those with fetal alcohol spectrum disorder (FASD) are the single most over-represented, under-recognized, and underserved group in the justice system. There are also concerns about human subject protection in research; alcohol abuse carries stigma which impacts Certificates of Confidentiality and informed consent. Judge Chezem concluded by asking if the alcohol research community is ready. People want justice system reform and they need alcohol research to make it happen.
Discussion: Dr. Koob suggested that the criminal justice system should be targeted in NIAAA’s strategic plan, but it should be. He and colleagues believe that lack of adequate education in medical schools is a culprit in the small percentage of people with alcohol disorder who get treatment and the even smaller percentage who get medication. He wondered if it would be useful to have a course on alcohol and substance use disorders in law school. Judge Chezem replied that such a course should be mandated, in her opinion; however, each state sets its own requirements. Dr. Koob asked Dr. Huebner to add this issue to the strategic plan as part of the focus on recovery. NIAAA should reach out to the criminal justice system about the availability of effective programs beyond Alcoholics Anonymous. Dr. DiClemente noted that a lot of treatment is being moved into the criminal justice system, but that nothing is available when people get out of prison. Drug and alcohol courts are a good idea, but only one piece of the puzzle. Judge Chezem replied that all courts are drug and alcohol courts and need information about effective treatment options.
Dr. Sinha stated that she would extend the requirement to all the areas of criminal justice, including parole and probation, because all components of the system need training. Given the big differences between states, she asked how NIAAA can address these disparate elements. Judge Chezem responded that she is working with the National Council of Juvenile and Family Court Judges and has worked with the National Association of State Judicial Educators and American Probation and Parole. These and other professional groups can open doors, but are not a total answer. Dr. Sinha also observed that no one is evaluating when a parent has FAS. Dr. Murray said that in the past at NIAAA, the myth was that the best place to get treatment was in prison where they were using what both NIAAA and NIDA recommended as treatment modalities. Judge Chezem responded that Bureau of Prisons probably does a better job than other places, but is still not a model for the diverse state systems. The National Institute of Corrections disseminates information about treatment in prisons to the State Departments of Corrections. Dr. Sinha asked if the prevalence of AUDs was assessed, e.g., does the household survey include people in the criminal justice system to assure they’re not underestimated? Dr. Warren responded it does not and Dr. Koob noted that there are difficult issues in recruiting from prison in the Adolescent Brain Cognitive Development (ABCD) study.
VA Ex-officio Members’ Reports
Dr. Dan Kivlahan gave his presentation via telephone. He reported that the VA/DoD Clinical Practice Guideline for Management of Substance Use Disorders is currently under revision; the draft Guideline will be available in October for external review. There is an emphasis on the full spectrum of severity, as well as the full menu of treatment options. The goal is to make the recommendations actionable and able to be tracked, then to address the implementation challenges of changing practices within the VA and Department of Defense systems. One emphasis involves pharmacotherapy; a recent analysis by VA researchers illustrated the challenges around the initiation of pharmacotherapy for alcohol use disorders. Using FY12 data, nearly 400,000 VHA patients had a documented AUD diagnosis. More than three-quarters of them also had a documented co-occurring mental health or tobacco use disorder. For those with co-occurring AUD and mental health disorders, the range of AUD pharmacotherapy was 7% to 11%, compared to medication for the psychiatric disorders which ranged from 69% to 82%. Even for a co-occurring tobacco use disorder, six times more people received medication for tobacco use cessation than did for alcohol use disorder cessation. Dr. Kivlahan is planning to develop a “one-pager” that would show the relative numbers needed to treat for those medications and those disorders. In addition to the treatment patterns, a broader issue is access. Congress passed the Veterans Access, Choice, and Accountability Act, which allows some veterans to get healthcare from non-VA doctors. The VA is having great difficulty in finding examples of non-VA care that are working well for veterans with alcohol or other substance use disorders, and in learning how to coordinate services within the VA system and with those in the community. Staffing in specialty care in the VA is relatively stable overall despite increases in clinical need, but workforce challenges include hiring and retaining enough addiction psychiatrists and other addiction medicine specialists. The VA is exploring the provision of tele-health to veterans with AUDs, but is experiencing issues in doing so, due to the workforce challenges.
Discussion: Dr. Koob encouraged Dr. Kivlahan to develop the document on numbers needed to treat and Dr. Robert Huebner indicated he would be happy to assist the VA in coordinating with NIAAA’s division of treatment. Dr. Koob emphasized this is an important issue and veterans are an important group with unique needs, so it will be valuable to increase the numbers of veterans with AUD who receive medication. He inquired about how programs will be evaluated. Dr. Kivlahan responded that the VA is using a tool called the Brief Addiction Monitor that covers a spectrum of recovery-related dimensions, including self-reported days of heavy alcohol use as well as days of drug use. The specific items on use have been incorporated into a number of other instruments used in the system, including the Veterans Outcome Assessment that is part of a telephone evaluation at the start of a new episode of mental health treatment and then at 90-day follow-up. Measurement-based care, which involves cooperative efforts between the veteran and the provider to get information in a timely way, is a complement to that. For example, some VA facilities are using the Brief Addiction Monitor at intake; and at least one reassessment 30 to 60 days afterward. Although useful, it is very cumbersome for data collection and entry because informatics tools to support the process are not yet available. Dr. McClain noted that the Choice Act system is problematic; in one NIH-funded study of patients with alcoholic hepatitis, those who are dying are the ones returning to alcohol abuse within one month. It’s important to get them into treatment. Dr. Kivlahan emphasized that patients need integrated care, rather than exclusively being sent to a specialty clinic.
Studying Both Sexes in NIH-funded Preclinical Research
Dr. Janine Clayton, Associate Director for Research on Women’s Health and Director of the NIH Office of Research on Women’s Health (ORWH), introduced the ORWH which is celebrating its 25th anniversary in 2015. The impetus for the creation of the Office was pressure from Senator Barbara Mikulski and others to include women in research studies, because findings from male subjects may not necessarily apply to women. Today, over 50% of participants in clinical trials and studies are women, with NIAAA having one of the strongest records among ICs. But each IC is different and general policies that work for all ICs are needed.
Males continue to dominate animal studies today. Fundamental biology is not only what is shared between males and females, but also what is different between them. The lack of reproducibility of many studies may be due to the absence of gender information in the reports. NIH has made a concerted effort to achieve its goal of balance in cell and animal studies. But policy implementation takes a team effort, including scientists, industry, and academic journals. For example, Dr. Tabak and others persuaded Science and Nature to require reporting the sex of animals in research articles. Changes to NIH policy on considering sex as a biological variable emerged after consultations with the ICs, NIH leadership, and others. In June 2015, NOT-OD-15-103, titled Rigor and Reproducibility, was released. It clarified and revised application instructions and review criteria to enhance reproducibility of research findings through increased scientific rigor and transparency. Among its requirements is that sex as a biological variable will be factored into research designs, analyses, and reporting in vertebrate animal and human studies. The new rules, pending approval by the Office of Management and Budget (OMB), will take effect for applications with receipt dates beginning January 25, 2016.
Dr. Clayton noted that sex, a biological difference, is not the same thing as gender, a social construct. To achieve NIH’s mission of turning discovery into health, different types of research—basic, preclinical, clinical, and medicine—require different considerations of sex as a variable. The new requirement is that researchers look at and report on sex differences in their studies. Between FY2013-FY2015, NIH invested $18 million to help researchers add what they needed to do to address sex differences in their studies. ORWH has supported FOAs related to sex/gender and health, such as an R01 on Women & Sex/Gender Differences in Drug and Alcohol Abuse/Dependence, as well as provided administrative supplements to NIAAA researchers.
To consider sex as a biological variable in their studies, investigators could add related search terms (e.g., sex, female, male) to their literature reviews, include both males and females in test groups, report sex-based data and any identified sex-based influences in their findings, and conduct pilot studies. Studies do not have to be powered to detect sex differences, but they do need to be reported, even if as a limitation of the study. There is a page (www.nih.gov/sexinscience) on the ORWH website that includes accredited online training with FDA to help researchers get started.
Discussion: Dr. Koob stated that he has committed to ORWH that each NIAAA division will develop a protocol for exploring sex differences related to alcohol in animal models. There is published research where the phenotype is the same between males and females, but different paths in how the brain gets there so there’s potential for interesting biological findings to emerge. Dr. Sinha asked how the Science and Nature editors responded and how the policy is progressing. She also wondered what CSR is doing to enforce the policy and how NIH could reassure preclinical scientists about the new policy. Dr. Clayton responded that the major issue among the journal editors was that sex-specific reporting would result in misunderstanding if the study was not powered for sex differences and the results showed no differences. NIH had to educate them that putting sex differences considerations into studies is important, e.g., if trials fail because sex differences weren’t initially considered, that’s an important cost. At CSR, Dr. Nakamura has been training study sections about how to apply these rules as part of their orientation training. It would be helpful to investigators if NIAAA divisions develop high-level sex differences protocols. Dr. Paul Kenny noted that including sex differences is valuable; his studies found large neurobiological differences in male and female animals, but they did not affect the behavior being observed. However, he can pursue additional funding to study the identified neurobiological differences. Dr. Molina asked how the scientific community at large will be trained to prepare their applications in accordance with the new requirements, e.g., by the provision of guidelines. Dr. Clayton responded that ORWH is partnering with OER to get the word out, but also need to partner with other organizations to do more. Dr. Adolf Pfefferbaum stated that it would be helpful to have some guidelines about when it is appropriate to power for detecting sex differences and when it may not be necessary. He also asked if there was a magnitude of difference that would indicate a sex difference. Dr. Clayton stated that NIH is trying not to be too prescriptive and suggested that researchers can figure that out based on their knowledge of their field. Dr. Pfefferbaum noted that study sections should be informed of this issue.
Developing the NIH-wide Strategic Plan
Dr. Lawrence Tabak, Principal Deputy Director of NIH, presented the development of the NIH-wide strategic plan. Development of the plan is mandated by the CROmnibus H.R. 83-346 law, which requires NIH to submit an NIH-wide 5-year scientific strategic plan to Congress no later than December 16, 2015. The pending 21st Century Cures Act would require NIH to develop and maintain a 5-year biomedical research strategic plan that identifies trans-NIH Mission Priority Focus Areas and includes both rare and pediatric diseases and the maintenance of the biomedical workforce as priorities. The plan should be a living document; it should not address priorities of the individual ICs, which are developing their own strategic plans.
Development of the plan began with NIH senior leadership and involvement of a working group from the ICs, including three representatives from NIAAA, who helped developed the plan and identified over 80 “call-out” examples. The plan has been reviewed by the NIH Advisory Committee to the Director (ACD), who advocated for additional emphasis on the interconnected nature of research and the inclusion of clinical methodologies, data science, and workforce retention. The NIH Director will oversee development of the final document.
The draft strategic plan consists of the following sections: Overview, Fundamental Science, Health Promotion/Disease Prevention; Treatment/Cures; Setting Priorities; and Enhancing Stewardship. The Overview includes the NIH mission and current NIH-supported research landscape. It also notes that this is a unique moment of opportunity in biomedical research, while also recounting the constraints facing the community in the face of lost purchasing power. The plan then identifies areas of opportunity that apply across fundamental science, health promotion/disease prevention, and treatment/cures. The discussion of each area of opportunity includes a succinct description of emergent opportunities, specific examples of recent breakthroughs (“Research Call-Outs”), alignment with the HHS Strategic Plan, and a consideration of NIH’s unique role within HHS. The plan concludes with a set of unifying principles that help NIH set priorities and enhance stewardship. The presentation of each unifying principle will include a description of the current status and/or emergent opportunities, specific examples of recent breakthroughs (“Stewardship Call-Outs”), and alignment with the HHS Strategic Plan.
To obtain input on the Strategic Plan, NIH has solicited feedback via a Request for Information (RFI), webinars, and consultation with the National Advisory Councils of 21 ICs through October. Approximately 1000 comments have been received to date. Broad suggestions are to emphasize implementation science, interdisciplinary science, peer review, workforce training, and systems approaches, as well as more explicit inclusion of behavioral and social sciences, basic vs. applied research, and patient partnerships. Other suggestions include promoting the use of big data and emphasizing population health.
Discussion: Dr. Koob suggested that NIH as the evidence-based source of information (e.g., NIAAA as the source of evidence-based information about alcohol) be emphasized in the report.
Dr. Messing proposed that an emphasis on innovation in grant submission be encouraged to allow unexpected findings to blossom. He also asked about the study of rare diseases. Dr. Tabak responded that studying a rare disease informs understanding of more common diseases and conditions. He also emphasized the important role of team science in studying rare diseases. Dr. DiClemente suggested including an emphasis on integration of care, treating the patient as a person rather than a problem. NIH has 21 siloed areas of problems. Working across them could help educate Congress about the importance of integrated care. Dr. Tabak responded that NIH doesn’t know how this will influence Congress, although it’s expected that they’ll read the last part on stewardship very carefully. There are fields, such as oncology, that have been transformed by molecular knowledge so that scientists now look for commonalities across pathways, not organ-specific diseases. NIH hopes this plan will resonate with the patient community and research community, but the agency also wants to reassure Congress. Dr. Sinha noted the importance of team science and interdisciplinary funding to provide integrated research, but asked if the plan would address a mechanism for making it happen. Dr. Tabak noted that NIH has taken modest steps in this direction, e.g., the Common Fund funds short-term experiments. Hopefully, IC leaders will consider interdisciplinary funding strategies in their strategic plans. Dr. Kenny suggested that resistance to disease be another area to include in the plan.
Ms. Pamela Walters, Al-Anon Family Groups, thanked Dr. Huebner for participating in a podcast on treatment options for loved ones of alcoholics on Al-Anon’s YouTube channel. She encouraged Council members to share a copy of the publication Al Anon Faces Alcoholism 2016 with others. Ms. Beth Keene Davidson from Community of Concern spoke on behalf of Mimi Fleury, its President and Cofounder. She thanked NIAAA for its work on Rethinking Drinking, and reported on how Community of Concern has disseminated the Rethinking Drinking booklet in Montgomery County, Maryland.
The meeting adjourned at 4:08 p.m.