National Advisory Council Meeting-February 7-8, 2007

National Advisory Council on Alcohol Abuse and Alcoholism

Summary of the 114th Meeting

February 7-8, 2007

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The National Advisory Council on Alcohol Abuse and Alcoholism convened for its 114th meeting at 5:30 p.m. on February 7, 2007, at the Fishers Lane Conference Center in Rockville, Maryland , in a closed session, and again at 8:30 a.m. on February 8, also in closed session.   The Council convened in open session at 9:09 a.m. on February 8.  Dr. Tina Vanderveen presided over the closed review of grant applications on February 7.   Dr. Ting-Kai Li, Director of the National Institute on Alcohol Abuse and Alcoholism, presided over the closed session on February 7; the closed session on February 8, at which the Board of Scientific Counselors Report was presented; and the open session the same day.

In accordance with the provisions of Sections 552b(C)(6), Title 5, U.S.C. and 10(d) of Public Law 92-463, the meeting on February 7, 2007, was closed to the public for the review, discussion, and evaluation of individual applications for Federal grant-in-aid funds.

Council Members Present:

Cheryl J. Stephens Cherpitel, M.P.H., Dr.P.H.

Victor M. Hesselbrock, Ph.D.

Joannes B. Hoek, Ph.D.

Gail A. Jensen, Ph.D.

Mack C. Mitchell, M.D.

Stacia A. Murphy

Stephanie S. O’Malley, Ph.D.

James W. Payne, J.D.

Kenneth J. Sher, Ph.D.

Alan C. Swann, M.D.

Boris T. Tabakoff, Ph.D.

Robert E. Taylor, M.D., Ph.D.

Hidekazu Tsukamoto, D.V.M., Ph.D.

Chairperson: Ting-Kai Li, M.D.

Executive Secretary: Abraham Bautista, Ph.D.

Senior Staff:

Vivian B. Faden, Ph.D., Ralph W. Hingson, Sc.D., M.P.H., Robin I. Kawazoe, George Kunos, M.D., Ph.D., Howard Moss, M.D., Antonio Noronha, Ph.D., Tina Vanderveen, Ph.D., Kenneth R. Warren, Ph.D., Mark Willenbring, M.D.

Other Attendees on February 8, 2007

Approximately 50 additional observers attended the open session, including representatives from constituency groups, liaison organizations, NIAAA staff, and members of the general public. Col. Joyce Adkins of the Department of Defense was also present.

Call to Order of the Closed Session, February 7, 2007

Dr. Tina Vanderveen called the closed session of the 114th meeting of the Council to order at 5:30 p.m. on Wednesday, February 7, 2007, for consideration of grant applications.   She reviewed procedures and reminded Council members of regulations pertaining to conflict of interest and confidentiality.   Members absented themselves from the discussion and evaluation of applications from their own institutions and in situations involving any real, apparent, or potential conflict of interest.   The closed session adjourned at 7:15 p.m.

Call to Order of the Closed Session, February 8, 2007

Dr. Li called to order the closed session at 8:30 a.m., during which Kathleen Grant, Ph.D., presented the Board of Scientific Counselors Report.

Call to Order of the Open Session and Introductions, February 8, 2007

Dr. Li called the open session to order on February 8, 2007, at 9:09 a.m. and welcomed participants.   Members of the Council, NIAAA staff, and audience members introduced themselves.

Director’s Report/Special Announcements/NIH Reform Act

Referring to the published “Director’s Report,” Dr. Li highlighted the following Institute activities:

§          NIH Reform Act.   The President has signed an omnibus reauthorization bill for the National Institutes of Health (NIH).   Among other issues, the law addresses funding and coordination of trans-NIH activities, how NIH is organized, and NIH rules for reorganization and creating new Institutes.

§          Budget.   Senate action was expected imminently on FY 2007 appropriations, as the government operating on a continuing resolution set to expire on February 15, 2007.   If the Senate were to concur with a House Appropriations Committee markup, NIH’s budget could increase slightly.   The President’s FY 2008 budget calls for a 0.2 percent increase over the FY 2007 budget.

§          Director’s activities.   Dr. Li attended a meeting of the Joint Commission on Science and Technology in Beijing, China .   China and the U.S. engage in good collaborative efforts on infectious diseases, among other areas, and China announced plans to triple its research support to investigate the effects of smoking, drinking, diet, diabetes, and hypertension.

§          NIAAA staff and organizational changes.   Peter Delaney, Ph.D., received the first-ever annual Legacy Award from the National Association of Deans and Directors of Schools of Social Work, and Peggy Murray, M.S.W., received the NIH Merit Award.   Ellen Witt. Ph.D. was recognized for her contributions to the Neuroepidemiology Blueprint Initiative.   Karen Peterson, Ph.D., has left NIAAA to join the National Institute of Biomedical Imaging and Bioengineering as Senior Advisor to the Director.   Abraham Bautista, Ph.D., now serves as NIAAA Executive Secretary.   Hee-Yong Kim, Ph.D., now heads the new intramural laboratory on molecular signaling; Bin Gao, Ph.D. and Dr. B.J. Song, Ph.D. have been appointed to editorships on major journals; and Klaus Gawrisch, Ph.D. has won the Avanti Award in Lipids from the Biophysical Society.

§          NIAAA research programs

 

• NIH Director Elias Zerhouni, M.D., visited NIAAA to learn about the Institute’s extramural research program.
• NIAAA is participating in the NIH Pathway to Independence Award Program, which combines postdoctoral fellowship training with the first support of researchers who enter an academic career track.   NIH has received 900 applications for the first three rounds.   NIAAA, which has funded Valentina Sabino of the Scripps Institute, will fund at least three investigators annually.
• In FY 2007 NIAAA anticipates a large number of RFAs, many competing renewals of alcohol center funding, and new applications for P50, P60, and P20 mechanisms.   Twenty people have applied for P20 funding.
• NIAAA has made decisions on 18 applications for the RFA on Underage Drinking and Building Health Care Systems response, with 4 funded.   Two grants are in rural and minority health areas; the National Center on Minority Health and Health Disparities co-funds two of the four awarded.  
• The new RFA Mechanisms of Behavioral Change has received 31 applications to date.   This program is a well-thought-out approach to minority areas of funding and has elicited interest in the research community.

§          Research reports.   Research publications by NIAAA-supported investigators have appeared in such journals as the Journal of Neuroscience, Alcoholism: Clinical and Experimental Research, and Proceedings of the National Academy of Sciences.   Dr. Li asserted that the quality of the journals reflects the quality of the research.

§          International activities.   NIAAA collaborates with other countries with the view that the alcohol problem is a global problem.   For example, France’s counterpart to NIH, INSERM, recently invited NIAAA to Paris to discuss possible collaboration with the Institute’s intramural and extramural programs.   Areas and mechanisms may include postdoc exchanges, collaborative laboratories and alcohol centers, and common areas of research interest, particularly neuroscience and the effects of alcohol on the brain and liver.  

§          Outreach activities

• The Leadership to Keep Children Alcohol Free has created a foundation, having recognized the need for long-term sustainability and independence from Federal contract monies.   The organization will receive support through grants and private contributions.  
• The Community of Concern, founded by Mimi Fleury to publicize the adverse effects of underage drinking, has grown from one school to a presence in 38 states and more than 300 schools.  
• Helping Patients Who Drink Too Much: A Clinician’s Guide, which has enjoyed strong global reception, has been updated with information on new medications.  
• NIAAA participated in the experimental Supercourse, an online library of lectures.   NIH and the National Library of Medicine have supported the program.   NIAAA’s lecture has been translated into Russian, Chinese, and Spanish.  

NIH Reform Act of 2006

Dr. Li reported that the President has signed the NIH Reform Act, and NIH has begun planning its implementation process.   The legislation establishes a Division of Program Coordination, Planning, and Strategic Initiatives to coordinate and fund trans-NIH initiatives.   When the so-called “common fund” reaches 5 percent—it is expected to grow with the NIH budget—Congress will evaluate the appropriate level of funding.   The legislation also creates a Council of Councils, an advisory board to oversee the process.   A Scientific Management Review Board will conduct periodic organizational reviews of NIH, and a public process for reorganization will be instituted.   The current 27 Institutes and Centers will remain intact until the Board convenes and determines changes in organization; the Board is to meet every 7 years.   The law provides authorization limits and simplifies some requirements for reporting to Congress.   NIH Deputy Director Raynard S. Kington, M.D., Ph.D., chairs a working group to analyze compliance with law and propose implementation plans.   Dr. Li suggested that the Research Society on Alcoholism may want to comment on the plans.  

Extramural Advisory Board Report: Division of Epidemiology and Prevention Research

Fulton T. Crews, Ph.D., Director, Bowles Center for Alcohol Studies, University of North Carolina–Chapel Hill, and Chair, NIAAA Extramural Advisory Board (EAB), presented the EAB’s portfolio recommendations for the new Division of Epidemiology and Prevention Research, the results of an August 2006 meeting to review the portfolio.

The EAB discussed enhancing measurement and trends in alcohol-attributable mortality, understanding alcohol-nutrition interactions across the lifespan, expanding screening and brief interventions in underage and young adult populations, and expanding comprehensive community interventions to reduce alcohol-related injuries and other problems.   The specific recommendations for priorities are:

1. Encourage systematic efforts to improve and standardize measures of patterns of alcohol exposure (acute, recent, or current history, and across the lifespan) and encourage their application across different grants, Institutes, countries, and the medical system.
2. Encourage research to improve measures of patterns of alcohol exposure (acute, recent, chronic) across the lifespan and their effects on morbidity and mortality.  
3. Improve estimation of alcohol attributable fractions (AAF) for morbidity and mortality, especially for injury, by better characterizing the relationship between patterns of drinking (e.g., binge drinking) and a variety of outcomes, and encourage the collection of relevant indicators of drinking (e.g., medical examiner data).
4. Replicate and generalize evidence-based environmental strategies developed in successful community trials and undertake pilot studies to develop new community strategies to address health and social outcomes.
5. Encourage culturally and developmentally appropriate screening, assessment, and interventions, especially brief interventions, and use creative technologies to maximize their reach, impact, and efficiency.
6. Use sub-studies or supplemental studies to: (a) enhance the fullest use of data and interdisciplinary research; (b) encourage the collection of biological and genetic samples from single-site or collaborative epidemiological, treatment, or human laboratory studies to develop new knowledge; and (c) promote the careers and training of emerging investigators.
7. Study promising strategies for preventing the early initiation of high-risk behaviors, including alcohol use through partnering with other agencies, Institutes, and organizations.
8. Undertake outcome studies of key alcohol and other relevant public policies (e.g., weapon, tobacco, drug, traffic, etc.) to determine if they reduce excessive alcohol consumption, related harms, or both.

Discussion.   Dr. Tabakoff stressed attention to individual differences, an under-represented area in current epidemiological research.   He urged use of existing knowledge about individual differences in looking at data and by subdividing the population to more biologically relevant cohorts.   Dr. Crews concurred, and Dr. Tabakoff observed the need to examine the trend from generalizability to individuality in future epidemiological studies.   Dr. Sher noted that the portfolio targets considerable genetic epidemiology and also research with a greater public health emphasis, reflecting alcohol’s burden on society; he observed a good balance of funding between the two points of view.   Dr. Hingson stated that the EAB’s review of the magnitude of alcohol morbidity and mortality shows most alcohol-attributable deaths are among young people, usually due to injuries, and account for twice the number of preventable years of life lost than chronic-disease deaths.   He acknowledged the need to include biologic measures in NIAAA’s research and noted that prevention epidemiology researchers have learning to do in this regard.  

Extramural Advisory Board Report: Strengthening Alcohol and HIV/AIDS Biomedical Research

Dr. Crews presented the EAB’s recommendations for strengthening alcohol and HIV/AIDS biomedical research, the results of a portfolio review at an October 2006 meeting.   He noted that grants for which NIAAA recommends funding are reviewed by the Office of AIDS Research (OAR). However, if OAR does not concur, the Institute is expected to seek non-AIDS funds to support these applications.  He observed that the public view of NIAAA’s research goals is not entirely clear, and that some infectious disease physicians do not routinely discourage drinking among AIDS-related patients.  

General themes included alcohol and HIV/AIDS biomedical research, natural history and epidemiology, etiology and pathogenesis, and prevention science.   The EAB set the context for the recommendations with a preamble:

§          Alcohol use and alcohol use disorders (AUD) are prevalent in HIV-infected individuals.   Individuals having both HIV and AUD represent a unique group that merits continued targeted investigation and intervention.   Past alcohol-related basic biomedical research has yielded valuable results related to HIV and AIDS that need further development and integration to be translated into prevention and treatment practices for at-risk and HIV+ populations with AUD.   This work is integral to understanding the AIDS epidemic among different indicated and targeted populations.   The following recommendations are focused on the biomedical aspects of the NIAAA HIV portfolio and are meant to complement (not replace) behavioral science-related efforts to improve the prevention and treatment of HIV/AIDS:

(a) Consider interaction among HIV, alcohol, and other comorbidities.

(b) Consider working across Institutes; include repositories.

(c) Consider joint mentoring and training.

§          Further research on the interactions among AUD, HIV, and other comorbidities is needed to advance understanding of the epidemiology, natural history, etiology, and pathogenesis (foundational areas) of all these disease endpoints separately and as a whole.   In particular, further development of a “bedside” to “bench” approach is needed to assure that basic (foundational) alcohol and HIV research is targeted to the most relevant aspects of HIV infection and progression to AIDS among individuals receiving or in need of care.  

§          It is critical that NIAAA work across Institutes to incorporate collection of information on alcohol use and AUD in ongoing and new, large, multicenter epidemiological and treatment studies and cohorts, including vaccine trials.   This includes access to repositories for biological specimens and DNA.

§          NIAAA should facilitate joint mentoring and training to encourage expertise in HIV and related fields such as expertise in chronic viral infections like hepatitis B and C, to be combined with alcohol expertise for the next generation of investigators.

The specific recommendations for priorities are:

1.        Organ and tissue injury .   Focus on key mechanistic targets for ethanol and HIV-induced injury to identify, measure, and prevent additive and interactive harmful effects at the cellular and organ systems level:

§         Brain injury and disease, including but not limited to neurocognitive and     neuroaffective deficits, peripheral neuropathy, and neural toxicities of HIV and HAART medication regimens
§         Anemia, bone marrow dysfunction
§         Liver disease (attributable to alcohol, hepatotrophic viruses, drug toxicities, metabolic disease)
§         Cardiopulmonary disease targets
§         Mitochondrial dysfunction as a common outcome of HIV and ethanol-related cellular injury
§         Nutritional effects of alcohol, HIV, and HIV therapy interactions with a special emphasis on the etiology of wasting

2.        Emerging pharmacotherapies .   Examine the pharmaco-kinetic and –dynamic effects of alcohol on current and emerging pharmacotherapies for the treatment of AIDS and AUD.   In addition identify how alcohol use and its treatment impact biomedical approaches to the prevention of HIV (e.g., antiretroviral drugs, vaccines, and microbicides, post-exposure prophylaxis) and associated comorbidities (e.g., hepatitis B and C, drug dependence, mental illness, neurodegeneration, cardiovascular disease, etc.).

3.        Targeted alcohol and HIV/AIDS populations .   Characterize unique aspects of alcohol/HIV interactions among women, children, adolescents, and older adults in domestic and international settings, and how these are moderated by racial, ethnic, and environmental factors.

4.        Viral indices and disease dynamics .   Examine impact of alcohol on viral indices (e.g., mutation accumulation and resistance), mucosal barriers, blood brain barrier, and immune responses and their impact on susceptibility, progression, and transmission of HIV.

5.        Animal models .   Develop cellular, systems-level, and animal models to study mechanisms underlying alcohol/HIV interactions and to identify effective approaches to translating findings from animal models to human models of alcohol/HIV interactions in the etiology and pathogenesis of AIDS (e.g., imaging in primates, in vitro cellular models of HIV replication, etc.).  

6.        Complex patterns of drinking .   Study the effects of longitudinal drinking patterns (including abstinence, withdrawal, and relapse) on HIV disease course (i.e., viral effects and immune effects), comorbid disease burden, development, and neurocognitive function.

7.        Coinfections and cofactors .   Determine mechanisms of alcohol-related immune dysregulation in HIV with and without coinfection (e.g., TB, HCV, etc.) and the impact of other comorbidities.   Consider the effects of cofactors, risk factors, and/or confounders associated with AUD and HIV transmission and progression, including but not limited to:

• Tobacco                                    
• Illicit drugs                                 
• Stress                                       
• Depression and other comorbid mental health disorders
• Co-occurring infections, including HCV and TB
• Other chronic medical illnesses
• Nutrition (particularly maternal/child and wasting)
• Genotypes (viral and host)
• Aging

8.        Comprehensive epidemic modeling .   Develop guiding integrative biological models in the areas identified above (areas 1-7) that highlight the multiple impacts of alcohol and to identify overarching complex constructs and processes predicting disease course and outcomes among HIV+ individuals with AUD (e.g., frailty, infectivity, rapid progression, etc.).   In particular, identify models that can predict the course of the epidemic and help to enhance the quality of care, especially related to the use of medications, and to improve treatment outcomes, including quality of life and survival.  

Discussion.   Dr. Kendall Bryant noted that NIH currently has 130 drugs in the pipeline at a cost of $2 billion; how alcohol will impact the drugs, and which will offer safer regimens, is an issue.   He added that modeling has shown that heavy drinkers, when on HAART therapy, have only half the life expectancy (10 to 12 years) of nondrinkers (20+ years), because heavy drinkers fail their regimen rapidly.   Dr. Crews asserted that comprehensive epidemiological modeling would show that heavy drinkers for biological reasons would get sicker, enabling establishment of alcohol as a morbid factor in this group.   Dr. Bryant emphasized strengthening the biological and biobehavioral issues important in looking at alcohol effects.  

Dr. Tabakoff inquired whether the Division investigates the various components of the envelope proteins, calcium dynamics, brain energy metabolism, and alcohol.   Dr. Bryant responded that NIAAA has conducted neuroimaging studies over the past decade, and that a program announcement is forthcoming that addresses those issues.   Dr. Crews noted that several ongoing human imaging studies show increased neurodegeneration, and the Institute is moving ahead with efforts to understand that interaction.   Dr. Bryant stated that NIAAA is trying to expand or continue studies on the blood brain barrier to look at potential effects of the damaging aspects of alcohol.   He clarified that NIAAA would not initiate animal studies, but that the Institute would study the effects of alcohol in ongoing studies.   He added that the Office of AIDS Research has expressed enthusiasm for this recommendation and currently is seeking appropriate representation on its review/expertise panels.  

Concurrence

Members of the Council expressed concurrence with both sets of EAB recommendations.

Center for Scientific Review: Challenges and Opportunities Facing NIH Peer Review, A Vision for Ensuring its Strategic National Value

Dr. Toni Scarpa, Director, Center for Scientific Review (CSR), NIH, stated that the U.S. Government spends a fraction per capita of what other countries spend on biomedical research, and all NIH research is peer reviewed.   By comparison, 2 percent of research in Europe, Australia, and Japan is peer reviewed.  

CSR receives all applications submitted to NIH—80,000 in FY 2006—of which it reviews 75 percent.   CSR engages 18,000 reviewers annually in a process managed by 250 scientific review administrators in 1,800 meetings per year.   NIAAA’s applications amount to about 1 percent of the total received and are assessed by 150 review groups, including special emphasis groups.   NIAAA had good results in FY 2003 because13 percent of applications from new investigators were assigned a percentile ranking of 10% or better. In FY 2006, NIAAA’s rate was slightly above average.  

Dr. Scarpa explained that while the U.S. military invented peer review, NIH has created the best academic medical centers and the best biomedical/behavioral research and biotechnology.   The process is never perfect, and major complaints focus on a slow process; too few senior/experienced reviewers; a process that favors predictable research instead of significant, innovative, or transformative research; clinical research that fares less well than other research; and burden to applicants and reviewers because of the time and effort required to write, submit, resubmit, review, and re-review.   The system was designed for far fewer applications; although NIH was built on investigator silos, research now takes place in the context of collaboration across continents and with big instrumentation; focus has shifted from unique diseases or organs to chronic problems, such as alcoholism and obesity, that affect all systems; and the character of the review groups has become more impersonal and overloaded.

A new vision of peer review begins with changing CSR operations, with a focus on increased transparency and communication, uniformity, and efficiency.   Dr. Scarpa observed 18 months ago that NIH accepted the paper equivalent of 81.2 acres of pristine forest in applications, three times a year, and then returned the equivalent amount of paper.   With its new technology, NIH now experiences virtually no problems with electronic transmission of R01 applications.   By June 2007 CSR anticipates it will enjoy considerable internal efficiencies related to assignment and dissemination of applications to reviewers.  

Dr. Scarpa summarized CSR’s vision for peer review reform:

1. Shorten the review cycle to permit timely resubmission of revised applications.   A successful pilot has led to planned implementation of the new system for all new investigators by November 2007.
2. Improve study section alignment and performance.   CSR has initiated a systematic biannual review of all IRG groups and study sections at monthly retreats.   CRS aims to make immediate improvements where possible and bring larger issues to the scientific committee, including Council.   To date CSR has created three new study sections and closed two due to obsolescence.   In addition CSR will sponsor six high-level workshops on the medical science to elicit input on the appropriateness of CSR’s reviews of the various disciplines and suggestions for improvement, and key questions or technologies relevant to the disciplines over the next 10 years, in order to inform planning.
3. Do more to recruit and retain more high-quality reviewers and decrease the burden on applicants and reviewers.   The number of applications received and the R01s and R21s CSR reviews has doubled in 5 years, requiring increasing numbers of reviewers.   Strategies include holding shorter meetings; requiring less travel by using electronic review, including telephone, video-enhanced discussions, and asynchronous electronic discussions (web chats); and shortening applications.  

The platform that produces the best review is the best platform.   Reviewers would convene in person once a year and via Internet for two other meetings that year.   The goal is to review 10 percent of all applications electronically in 2007. This will amount to 5,000 applications.   The advantages of shorter applications include increased ability for each reviewer to read more applications; study sections can be smaller; more experienced reviewers can be recruited; and reviews can focus more on impact and innovation, and less on approach and preliminary results.  

The goals of the Trans-NIH Committee to Shorten the Application include a focus on the R01, consideration of reducing the page limit, and aligning the application more closely with review criteria.   Councils and scientific leadership have shown strong support for the goals.  

Dr. Scarpa commended NIH’s SRAs and the 100,000 scientists who work 2 months a year for $200 a day for 2 days.   In terms of national value, peer review has identified risk factors, treatments, and cures for coronary heart disease, for example, which has prevented 1 million deaths incrementally every year.   Each year Americans spend less than it costs for a latte to save 1 million people.   Millions of Americans have been cured or are in remission because peer reviews identified the best cure or therapy for various diseases.  

Discussion.   Dr. O’Malley inquired whether terms on study section would help to recruit more senior, experienced investigators.   Dr. Scarpa suggested that recapturing intellectual stimulation at meetings might serve as an incentive, as well as serving longer terms, but attending few meetings each year.   Other strategies under consideration are abolishing application deadlines and extending grant support to compensate for time investigators spend working on reviews.   Dr. Tabakoff supported abolishing deadlines and instituting a rolling review process similar to approaches taken by editorial boards that review potential journal articles.   Dr. Scarpa stated that such a process is under consideration for fellowships.   A particular grant is submitted 2.1 times on average, and Dr. Mitchell suggested that perhaps greater burden should be placed on institutions prior to submission of applications to NIH for review, as is done with IRB on animal safety, for example.   Dr. Scarpa responded that with some Institutes paying below the 10th percentile, the problem is the opposite—a grant cannot be any more improved.   CSR is considering giving two scores, one to reflect the potential of the application if all were perfect.   He stated that a pilot of a shorter application probably will be conducted.   Dr. Li stated the importance of sufficient budget to fund the grants.  

Research Society on Alcoholism’s Research Priority Committee Report

Dr. Kathleen Grant, President, Research Society on Alcoholism (RSA), and Professor, Oregon Health and Science University , discussed recommendations for research priorities that RSA hopes may produce a useful tool for NIAAA.   Dr. Grant explained that the draft recommendations are intended to complement the EAB’s recommendations with views from scientists who may be embarking on their careers.  

Committee members listed selected areas for alcohol research (training, basic, translational, trans-Institute, clinical/social/epidemiological, and new tools) in four categories: present and high priority, present and underfunded, new and high impact, and new and unknown impact.   For example, RSA committee members recognized that NIAAA is funding training, so no new funding is needed; but they identified areas of high priority and areas that are underfunded.   Dr. Grant welcomed NIAAA input, perhaps including a NIAAA representative on the committee, to ensure that research suggestions are categorized correctly and to identify misperceptions about the research that NIAAA currently funds.   One theme that emerged is the need for standard operating procedures for imaging.   Dr. Grant invited feedback from Council members regarding the potential usefulness of this process.

Discussion.   Dr. Li suggested that NIAAA might work with RSA to plan a method and venue—perhaps a program for postdocs at the next RSA meeting—to inform the field about the types of research the Institute funds.   Dr. Grant stated that the RSA meetings offer a number of possibilities.   Dr. Li tacitly suggested the need to publicize NIAAA’s website and strategic plan.   Dr. Hoek suggested that RSA organize its list of NIAAA programs to create categories that recognize the broader science that applies to alcohol.   He noted that the EAB brings in outside experts, and communication between RSA scientists and the EAB would be useful and should be encouraged.   Dr. Li offered to work with RSA on a program at the next RSA meeting.  

Compliance with Inclusion Guidelines

Bridget Williams-Simmons, Ph.D., Emerging Leader Intern at NIAAA, explained that the NIH Policy on the Inclusion of Women and Minorities as Subjects in Clinical Research mandates that women and members of minority groups and their subpopulations must be included in all NIH-funded clinical research, and that exclusion may be made by the IC Director or NIH Director based on compelling rationale and justification.   Cost is not an acceptable reason for exclusion, and NIH must support outreach efforts to recruit and retain women and minorities.

Every 2 years each Institute’s Advisory Council prepares a report on compliance with the inclusion policy to be included in the NIH Director’s biennial report to Congress.   Dr. Williams-Simmons enumerated NIAAA procedures to ensure compliance and presented inclusion data highlights for FY 2005 and 2006.   Enrollment of females and minorities in clinical research was relatively consistent, while enrollment in Phase III clinical trials dropped significantly, due to completion of one large trial.   Numbers remained consistent in clinical trials for race and ethnicity, as did the numbers for Phase III trials; because the number of protocols was reduced from two to one, some declines in ethnicity were experienced.

Dr. Li acknowledged that the report has been presented to Council.  

Interventions for Suicidal Patients with Co-occurring Alcohol Use Disorder

Barbara Stanley, Ph.D., Director, Suicide Intervention Center, Columbia University , explained that her center focuses on pharmacological and psychosocial interventions for people who are at risk for suicide, classification and identification of at-risk individuals, tracking of high-risk individuals, and treatment engagement.   Research questions regarding co-occurring alcohol use and suicide behavior include: Does alcohol increase the risk for suicidal behavior? Is targeted intervention research that focuses on the co-occurrence of alcohol and suicidal behavior necessary? Can established interventions be applied to this population? Do novel interventions need to be developed?

Dr. Stanley reported that more than 32,000 suicides occurred in the United States in 2004.   For people under age 65, suicide is the fourth leading cause of death, the second among people ages 25-34, and third among ages 10-24.   More than 500,000 emergency department (ED) visits in 2003 resulted from self-inflicted injury, and a possible increase in youth suicide occurred in 2005.   Suicide ranks fourth as a leading cause of premature death; liver disease ranks eighth; and HIV ranks tenth.   Comparatively few funds are devoted to suicide research.

Alcohol plays several roles in suicidal behavior: AUD as a risk factor, a means of suicide or attempted suicide, a means of disinhibiting behavior—to give courage to make the attempt—and nonsuicidal persons becoming suicidal in a binge-drinking context.   One or several of these roles can affect a single person.   Most research examines alcohol and suicide as risk factors.   Such studies have found, in a sample of men free of cancer for several years, that quantity of alcohol consumed per drinking day is associated with greater risk of suicide mortality, although drinking frequency and binge drinking are not; in an epidemiological study of mental illnesses, alcohol dependence had a suicide risk at a level above and beyond major depression; early substance abuse in adolescent boys, and heavy drug use, getting drunk, and cigarette smoking at an early age in adolescent girls is related to suicidal behavior.   Available data show that 45 percent of attempters with borderline personality disorder have co-occurring AUD; however, alcohol is rarely spoken about in relation to this population.   In persons with major depressive disorder, 37 percent have co-morbid AUD, and co-morbid AUD occurs in 42 percent of persons with bipolar disorder.   Suicide attempters with AUD, compared to other suicide attempters, are a more impaired group with more stressful life events, double the number of depressive episodes, earlier onset of depression, earlier psychiatric hospitalization, and increased incidents of child abuse and other adverse characteristics.   Persons with co-occurring AUD experience more difficulty on virtually every factor.  

Research indicates that high co-occurrence of suicidal behavior and AUD may be linked to shared genetic traits, shared serotonergic dysfunction, or an environmental co-occurrence.   Alcohol plays a direct role in about a third of suicide deaths annually; it is the substance most frequently tested for and is present much more frequently than any other substance at death.   In the Conti Center ’s database, alcohol as a means for suicide was used by 17 percent of attempters, in 8.7 percent of attempts.   Alcohol tends to be combined with other substances, and individuals who use alcohol as a means tend to make multiple suicide attempts; the 45 subjects with AUD made 155 attempts. Alcohol tends to increase the lethality of suicide attempts.   Findings indicate the need for physicians to ask patients whether they used alcohol as way to make decisions about their attempts.  

Dr. Stanley reported that few studies guide intervention efforts for persons with AUD and suicidality.   Use of Fluoxetine and cognitive behavioral therapy (CBT) both have shown promise.   The Suicide Intervention Center is working to develop new targeted interventions and applying already-developed interventions with some established efficacy in this population.  

A review of exclusion/inclusion criteria on suicidality, alcohol dependence and abuse, substance abuse disorders (SUD), and psychosis in 77 trials conducted on Fluoxetine, Citalopram, Paroxetine, and Sertraline from 1984 to 2001 was conducted.   It showed that 47 of the trials were silent on whether acute suicidality or past or recent suicidal behavior served as an exclusion.   Thirty-five first authors of the 47 trials responded to an inquiry by e-mail or phone, but no additional information was found for 12 studies.   With regard to inclusion/exclusion of suicidal patients, only 8 of 77 trials included some level of suicidality, with no separate subanalyses.   With regard to SUD, the preponderance of studies excluded AUD and/or SUD.   It is possible to conclude that existing studies may or may not be generalizable because of the restricted inclusion/exclusion criteria.   Regarding current SSRI issues in adolescents and young adults, Dr. Stanley asserted that if these trials had included the population destined to use the medications, outcomes might have been different.

Several center projects are investigating existing and novel treatments, for example: (1) a study of Fluoxetine versus Bupropion to reduce impulsivity and suicidal ideation in persons with major depression and AUD, and (2) a modular psychosocial brief intervention targeted to suicidal college students, mainly Latino, with co-occurring binge drinking, using a CBT approach with problem solving, targeting suicidal cognition and skill enhancement, and referral services.   Preliminary results include significant decreases in suicide ideation and depression, trends toward decreased hopelessness and anxiety, and high student satisfaction.   The center’s ongoing treatment trials investigate dialectical behavioral therapy versus supportive treatment and Fluoxetine versus a placebo in suicidal individuals with borderline personality disorder, and lithium versus Valproate in bipolar suicide attempters.   The studies are now enriching their samples for co-occurring AUD to investigate differences.

Dr. Stanley discussed method enhancements needed to conduct suicide intervention trials.   (1) In terms of engagement strategies, a large number of suicidal individuals either do not seek mental health treatment or, after an ED visit for suicidal behavior, never follow up on treatment; the sex difference in treatment seeking is alarming; males are less likely to seek treatment and more likely to commit suicide.   The center is developing a pilot project to develop and test in the ED a motivational enhancement intervention to engage suicidal individuals to consider treatment that could be adapted to accommodate ethnic differences.   (2) A suicide attempt registry to classify, record, and track suicidal behavior systematically could help determine if large‑scale prevention efforts are effective.   The American Foundation for Suicide Prevention and the University of Pennsylvania have funded a pilot project.   The University of Rochester may implement a suicide attempt registry in the center’s EDs.   Dr. Stanley noted that in addition to being a risk factor for completed suicide, attempts reflect morbidity in and of themselves.   (3) In terms of proxy measures for improvement in suicidality, research that uses suicide and suicide attempts as outcome variables requires large samples.   As an alternative to suicide attempt registries in which every suicide attempt is tallied, proxy measures that track well with suicidal behavior can serve a useful function.   The center has developed a Suicide Assessment Scale with good reliability that differentiates attempters from nonattempters.   A pilot project will test the scale at the time of the attempt and follow people in time to see if the scale measure declines.   (4) Accurate and reliable classification of suicidal behavior is needed.   Dr. Stanley related a series of dramatic examples of misclassification of suicide attempts revealed in the FDA Reclassification Project.   The center is developing tight definitions, for example, distinguishing between ideation and behavior and between suicidal and nonsuicidal self-injurious behavior.  

Discussion.   Dr. Mitchell inquired about classification of single-car, single-occupant traffic accidents with alcohol involvement.   Jane Pearson, Ph.D., of the National Institute on Mental Health, and Chair, Suicide Research Consortium, suggested that studies look at death certificates, noting that when coroners use more consistent definitions, more suicides and fewer unidentified deaths will be reported.   Dr. Stanley’s group requires evidence of suicide for classification.   Dr. Li inquired about the average tissue alcohol concentration in completed suicides and the number of drinks that attempters use as a method.   Dr. Stanley replied that she will answer the first question by e-mail and that she is unaware of data on the number of drinks.   Dr. Pearson noted that trauma surgeons have a registry for number of drinks.   Dr. Stanley observed the debate in the field on how to define a suicide attempt—whether or not it is intent based.   Dr. Pearson added that the level of impairment plays into the question of cognitive intent, particularly among American Indian tribes with their high-level of binge drinking or poisoning, and among consistent drug users who probably know their level and then overdose.   To a question from Dr. Cherpitel, Dr. Stanley stated that the center intends to expand the college suicide study to campuses with larger Caucasian populations.   She noted that young Black males in their early 20s and older white males are at high risk.   Dr. Pearson added that primarily men die by suicide, particularly middle-aged and older white men, and white women.   Suicide attempts are high among young Latina women.   Dr. Stanley responded to a question from Dr. Tabakoff that women make more suicide attempts and males are more prone to die by suicide.   Dr. Moss noted that certain researchers have conducted elegant post-mortem neurochemistry on individuals who were alcoholic and had completed suicide.   Dr. Stanley noted that she and these researchers work closely together.   She replied to Dr. Moss that brains cannot be collected in New York State, but that brain samples are collected from Macedonia .   Dr. Hingson suggested that it would be interesting to see whether any states consistently test all suicides for alcohol.   For a relatively small financial investment, one could determine whether alcohol-related suicides are declining and whether various alcohol policies have an effect.   He noted that 20 states have no laws requiring withholding of Medicaid reimbursement for people who have been injured under the influence, and other states are repealing such laws.   He added that trauma centers now require screening for alcohol as a condition for accreditation.   He stated that a meta-analysis of alcohol treatment studies has found that participants who reduce their drinking have reduced suicide rates.  

Consideration of the September 2006 Minutes and Future Meeting Dates

Council members voted unanimously to approve the minutes of the Council meeting of September 20-21, 2006.   Upcoming Council meetings will take place on May 23-24, 2007, September 12-13, 2007; February 6-7, 2008, June 4-5, 2008, September 17-18, 2008; February 4-5, 2009, June 10-11, 2009, September 16-17, 2009; and February 3-4, 2010, June 9-10, 2010, September 15-16, 2010.  

Council Member Round Table                                                

Dr. Hoek stated that while the alcohol field is losing half a generation of researchers, he is impressed with the way NIAAA has addressed the issue.   Dr. Li responded that he takes responsibility for efforts to reach down the pay plan for new investigators.   Dr. Hoek pointed out that another group at risk in terms of career investment includes people who have received a round of R01 support and who are coming up for competing renewal; if they lose their job, they risk finding a satisfying career and remaining in the field.   Dr. Li responded that staff pays attention to this group, as well as, not-so-young investigators with A2 grants, who, if they lose their funding, lose their laboratories.

Ex-officio Member and Liaison Representative Reports, and Public Comment                     

Marie Gallo Dyak, Executive Vice President, Program Services and Government Relations, Entertainment Industries Council, Inc., expressed appreciation for NIAAA’s presentation on alcohol abuse and suicide.   She urged continuing this kind of research, in conjunction with efforts to look at onscreen depictions of suicide.

Mimi Fleury, founder, Community of Concern, extended thanks to NIAAA and its staff for support for publication and dissemination of the organization’s brochure "A Parent's Guide for the Prevention of Alcohol and Other Drug Use," which educates parents on the science regarding underage drinking.   She noted that Dr. Li and Dr. Hingson both made well-received presentations to the local community.  

Col. Joyce Adkins from the Department of Defense expressed appreciation for the opportunity to be considered for ex-officio membership and to serve in this council She also anticipates linking Department of Defense activities with NIAAA’s work.

Adjournment

Dr. Li adjourned the meeting at 2:20 p.m.

CERTIFICATION

I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.

/s/

Ting-Kai Li, M.D.

Director

National Institute on Alcohol Abuse
and Alcoholism
Chairperson

National Advisory Council on Alcohol Abuse and Alcoholism

/s/

Abraham Bautista, Ph.D.

Chief,

Extramural Project Review Branch

and

Executive Secretary

National Advisory Council on Alcohol Abuse and Alcoholism