The National Advisory Council on Alcohol Abuse and Alcoholism (NACAAA) convened for its 100^th meeting at 7 p.m. on June 5 at the Pook's Hill Marriott Hotel in Bethesda, Maryland, and at 8:35 a.m. on June 6 in Conference Room E1/E2 of the Natcher Conference Center, Building 45, on the campus of the National Institutes of Health (NIH) in Bethesda, Maryland. Dr. Kenneth R. Warren, Acting Executive Secretary and Director of the Office of Scientific Affairs, presided over the closed session on June 5 and Dr. Raynard S. Kington, Acting Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), chaired the open session on June 6.

In accordance with the provisions of Sections 552b(C)(6), title 5, U.S.C. and 10(d) of Public Law 92-463, the June 5 meeting was closed to the public from 7 to 9 p.m. for the review, discussion, and evaluation of individual applications for Federal grant-in-aid funds. The meeting on June 6 was open to the public from 8:35 a.m. until the 3:35 p.m. adjournment for discussion of program and policy issues.

Anna Mae Diehl, Ph.D.
Steven M. Mirin, M.D., Ph.D.

Ex-Officio Council Members:

Richard T. Suchinsky, M.D., Department of Veterans Affairs

Approximately 133 additional observers attended the open session, including representatives from constituency groups and liaison organizations and NIAAA staff as well as members of the general public.

Dr. Kenneth R. Warren, Director of the Office of Scientific Affairs, NIAAA called the closed session of the 100^th meeting of the NACAAA to order at 7 p.m., June 5, for consideration of grant applications.

Dr. Kenneth R. Warren, Director, Office of Scientific Affairs, reviewed the procedures for the conduct of grant application review, and reminded the Council members of the regulations pertaining to conflict of interest and confidentiality.

Members absented themselves from the discussion and evaluation of applications from their own institutions, or in situations in which a potential conflict of interest, real or apparent, might occur.

Council members concurred with all initial review committee recommendations for all grant applications available to them. Council members also concurred with the MERIT extension applications. Council did not review applications that were "Not Scored" or with a percentile score of 40 or higher.

Dr. Raynard S. Kington, Acting Director of the National Institute on Alcohol Abuse and Alcoholism, called to order the open session of the 100^th meeting of the National Advisory Council on Alcohol Abuse and Alcoholism at 8:37 a.m. on June 6. In welcoming remarks, Dr. Kington took note of the milestone occasion and invited those attending to partake of a special celebratory cake during the morning break.

After noting that Council member, Dr. Anna Mae Diehl, was unable to attend the meeting, Dr. Kington introduced two new Council members. Ralph W. Hingson, Sc.D., M.P.H., Professor and Associate Dean for Research in the Department of Social and Behavioral Sciences at the School of Public Health, Boston University School of Medicine, has published widely on fetal substance exposure, prevention issues, traffic safety, survey methodology, and statistical techniques. He conducted a landmark study comparing outcomes for alcoholism treatment among Employee Assistance Programs and most recently served on the Council's College Drinking Task Force for which he authored the well-received primary analytic study.

Howard J. Edenberg. Ph.D., Professor of Biochemistry and Molecular Biology and of Medical and Molecular Genetics at the Indiana University School of Medicine, is a leading geneticist who participated in the Cooperative Study on the Genetics of Alcoholism (COGA) which identified chromosomal regions where genes contributing to alcoholism vulnerability will likely be found.

Before outlining activities undertaken by NIAAA since the February Council meeting, Dr. Kington reported on several previously discussed plans. No further action was taken toward conduct of a potential National Academy of Sciences’ study on merging NIAAA and NIDA into a single National Institute on Addictions. However, a congressionally mandated study by a committee of the National Academy of Sciences has begun assessing the feasibility of reorganizing the institutes within the NIH. This study, to be chaired by Dr. Harold Shapiro, a past President of Princeton University, had been postponed pending appointment of a new NIH Director—which has now occurred.

The deadline for accepting applications for a new NIAAA Director has closed and the search committee has met twice, purportedly to winnow the candidates. Initial interviews and assessments will likely occur within the next several months. The search is proceeding in tandem with two related ones for new Directors of NIMH and NIDA.

Referring to his formal Report on Institute Activities, Dr. Kington highlighted a number of key activities and accomplishments.

Dr. Ruth Kirschstein, Acting Director of NIH, presented the FY 2003 President’s budget request for all NIH Institutes and Centers to House and Senate appropriations subcommittees in March. Dr. Kington testified as part of a combined hearing with other Institute Directors on the theme of Disease Prevention and Health Promotion. To-date, neither the House nor the Senate has scheduled markup hearings, and no further progress toward budget approval has been reported.

As a result of usability testing last fall, several changes are being made to NIAAA’s Web site and new items added (see page 2 of the Director’s Report). The site Director, Ms. Diane Miller, and her staff are beginning a second testing phase that will likely result in more changes. Participants in the first test phase found the Web site very accessible and useful to the public.

A new NIH Director, Dr. Elias A. Zerhouni, was appointed and confirmed on May 2, with extensive media coverage of his administrative and scientific accomplishments. Dr. Kington, after meeting Dr. Zerhouni in a group with other NIH Institute and Office Directors, lauded his knowledge of issues as well as his openness and managerial abilities. A one-on-one meeting to discuss NIAAA is being scheduled, and other group meetings on selected topics are underway, including the first meeting of an Advisory Committee to the Director.

A NIH Consensus Development Conference entitled Management of Hepatitis C: 2002 is scheduled for June 10-12 to review the history, epidemiology, and current therapies for this disease as well as to identify directions for future research. Dr. Diane Lucas, Division of Basic Research in NIAAA, organized a Working Group on Hepatitis C and Alcohol to be held in conjunction with the Consensus Conference that will focus on issues related to treating HCV-positive individuals who abuse or are dependent on alcohol.

In April, Dr. Kington and Ms. Kelly Green Kahn, Public Liaison Officer for NIAAA and Co-chair of the Office of Public Liaison (OPL) Health Disparities Workgroup, participated in discussions with members of the Council of Public Representatives (COPR) on the social and cultural dimensions of health. COPR has drafted a Health Disparities Outreach Kit that members can use in planning local and regional activities. COPR is an exemplary cooperative endeavor by scientific staff in the Institutes and public representatives to disseminate research results widely.

The NIAAA and the National Organization on Fetal Alcohol Syndrome (NOFAS) launched a Fetal Alcohol Syndrome (FAS) Awareness Campaign in March that targets African American women of childbearing age in the District of Columbia, a group consistently found to be at high risk for bearing FAS-affected children. The prototype pilot campaign, Play It Safe: Alcohol and Pregnancy Don’t Mix, expects to reach not only African American women, but also their relatives and influential friends with media messages, special events, and community partnership activities.

The College Drinking Initiative published the landmark College Task Force Report on April 9. Before this widely publicized event, NIAAA staff presented the findings to representatives from other Institutes, the Centers for Disease Control and Prevention, and the Office of National Drug Control Policy. Although Dr. Kington’s written report states that staff met with the Secretary of Education, Ron Paige, he was actually briefed by a member of the Task Force, President Lyons of California State University. Dr. Kington also testified with Drs. Goldman and Hingson at a Senate Governmental Affairs Committee hearing, chaired by Senator Lieberman, on the binge-drinking epidemic on college campuses.

The College Task Force Report, which packages a remarkable amount of scientific information for a wide variety of audiences, is being sent to every college and university in the United States along with other specially-developed drinking prevention materials. As a result of sweeping media coverage, an estimated half of the American public were alerted to the document’s findings. The positive response reflects the Nation’s serious concern with drinking and its consequences among college students. The Report can be accessed at www.collegedrinkingprevention.gov.

The annual National Alcohol Screening Day, April 11, was coordinated by Ms. Peggy Murray and Dr. Anton Bizzell from NIAAA’s Office of Collaborative Research. Many activities for this successful event were planned in tandem with College Drinking Initiative efforts. The targeted populations included the elderly, Hispanic-speaking persons, and urban minority groups. The number of participating sites more than doubled over the last 3 years to a total of 2,825 in 2002.

The annual Senator Harold Hughes Memorial Award for 2002 was given to Barbara Foley, R.N., Executive Director and Co-founder of Emergency Nurses CARE (EN CARE) of Alexandria, Virginia. Ms. Foley has been invited to attend a future Council meeting.

As pages 8-10 of the Director’s Report note, Governors' spouses are working to increase the visibility of underage drinking through the Leadership to Keep Children Alcohol Free Initiative.

The Health Disparities Strategic Plan for FY 2002 - FY 2006, which was presented to the February Council meeting, will soon be released and is available at the National Center for Minority Health Disparities’ Web site (see http://ncmhd.nih.gov/).

As a result of a 2001 RFA, NIAAA now funds eight exploratory/developmental grants through the R21 mechanism to stimulate research on malt liquor and related products. In response to parents’ and the public’s concerns about alcopops and similar malt beverages, NIAAA expects the research to reveal more about the impact of these drinks on younger persons and the marketing strategies used to increase children’s alcohol consumption.

Recipients of 15 exploratory/developmental grants on the role of spirituality in preventing alcohol abuse and maintaining sobriety met for the second time on May 30-31. Dr. Kington attended the event with representatives from the other co-sponsor of the grants, the Fetzer Institute in Kalamazoo, Michigan.

In response to issues raised at the February Council meeting, NIAAA formed a working group of experts to help develop research targeted at alcohol-related health issues affecting Hispanic citizens as well as to enlist more Hispanic researchers in this endeavor. A meeting of the group, scheduled for June 24, includes former Council member, Dr. Marilyn Aguirre-Molina, Dr. Carlos Molina, Dr. Jeannette Noltinus, Dr. Bill Vega, and Dr. Andreas Gill.

Through the Office of Policy and Public Liaison, NIAAA is supporting several collaborations designed to disseminate alcohol-related research findings through such relevant organizations as the Parents’ Resource Institute for Drug Education (PRIDE), the National Association of State Alcohol and Drug Abuse Directors (NASADAD), the American Association for Marriage and Family Therapy (AAMFT), and CSAT’s Practice Improvement Collaboratives Program.

Dr. Lorraine Gunzerath chaired an NIAAA-sponsored workshop in May on alcohol-related gene-environment interactions that also entailed coordination with staff from the Institute’s Offices and Intramural and Extramural Divisions (the summary is a later agenda item).

Several new public information materials have recently been released. NIAAA and the NIH Office of Research on Women's Health jointly produced a video for distribution to treatment providers serving women with drinking problems (see later agenda item). A Spanish-language version of the booklet, Frequently Asked Questions, has been printed and distributed, as has a poster targeting underage drinking that was developed by NIAAA in partnership with CSAT. The poster debuted during an Alcohol Awareness Month Make a Difference campaign in Colorado chaired by First Lady Frances Owens (see http://pubs.niaaa.nih.gov/publications/poster.htm).

Page 21 of the Director’s Report lists upcoming workshops or symposia that were organized by or have planned participation by staff from the Division of Basic Research. Three recently released RFAs/PAs on genotyping, stem cell research, and cellular and molecular mechanisms related to alcoholic hepatitis are also described on page 22, with information on staff contacts.

Drs. Noronha and Zakhari organized a well-received April symposium on genetics and alcoholism as part of the annual conference of the American Society of Addiction Medicine (ASAM). The purpose was to educate busy clinicians about such basic research topics as human alcoholic phenotypes and discoveries by COGA that may lead to improved patient treatment.

During the 2002 Brain Awareness Week in March at the National Museum of Health and Medicine in Washington, D.C., the Drunken Brain exhibit designed by NIAAA’s Dr. Dennis Twombly was a popular success, particularly with the more than 400 student visitors. Other demonstrations in different venues for younger children were also enthusiastically received.

The Division of Clinical and Prevention Research recently sponsored two well-attended workshops: one in May for basic scientists and clinical researchers on alcohol and tobacco co-dependence; and another in March on medications development for NIAAA-funded clinical researchers, staff, and pharmaceutical industry representatives.

There were two activities conducted by the Health Services Research Branch aimed to bridge the gap between research and practice. A working group meeting on April 19, collected providers’ suggestions about research priorities the Institute should encourage, and a North Carolina Researcher-in-Residence project is using technical assistance visits by a leading researcher to convince treatment clinics to adopt evidence-based improvements in their practices.

The Division of Intramural Clinical and Biological Research (DICBR) was involved in several noteworthy activities (see pages 32-39). Among these was the Benedict J. Latteri Memorial Scientific Symposium in May on Ion Channels and Synaptic Transmission. The eight distinguished scientists who lectured at this event were a fitting tribute to the remarkable achievements of Mr. Latteri, Acting Deputy Scientific Director of NIAAA from 1998 to 2001.

DICBR also appointed two highly respected scientists as staff. Stephen R. Ikeda, M.D., Ph.D., was hired as a Tenured Investigator and Chief of the Laboratory of Molecular Physiology. A widely published pharmacologist, Dr. Ikeda was most recently a Tenured Associate Professor of Pharmacology and Toxicology at the Medical College of Georgia, Senior Scientist in the Laboratory of Molecular Physiology at the Guthrie Research Institute, and Director of the Guthrie cDNA Resource Center. His new NIAAA laboratory will investigate molecular mechanisms underlying neurotransmitter-mediated modulation of voltage-gated ion channels and extend previous work on CNS synaptic systems.

David M. Lovinger, Ph.D., a cellular neuroscientist, also joined DICBR as a Tenured Investigator and Chief of the Laboratory for Integrative Neuroscience. His laboratory will focus on assessing the role of particular molecular targets of alcohol in acute intoxication and alcohol-seeking behavior, analyzing membrane proteins that are targets for alcohol actions, creating and providing transgenic and mutant mice, and developing electro-physiological and structural biological analysis techniques for researchers at other institutions who are examining alcohol's effect on target proteins or neurons. Dr. Lovinger was formerly Professor of Molecular Physiology and Biophysics and Pharmacology at the Vanderbilt University School of Medicine, as well as Deputy Director for Biomedical Research at Vanderbilt University’s Kennedy Center.

After announcing changes, detailed on pages 40-42 of his formal report, involving eight staff positions (i.e., Mr. Roger Hartman, Dr. Sathasiva Kandasamy, Dr. Mahadev Murthy, Dr. Karen Peterson, Dr. Robert Freeman, Ms. Elsie Fisher, Ms. Jane Binakonsky, Ms. Virginia Wills) and calling attention to eight other DICBR term appointments, Dr. Kington mentioned the following special honors conferred on Institute staff and activities.

• Staff on the "College Team" received an NIH Director's Award for creating a college drinking prevention initiative that promotes health and saves lives.
  
  
• Since its launch, the Web site at has received numerous awards for excellence, and the list continues to grow. The student section features an interactive virtual body showing alcohol’s impact on different organs.
  
  
• Dr. Gayle Boyd, Prevention Research Branch, Division of Clinical and Prevention Research, shared a 2001 NIH Plain Language Award with Ms. Diane Miller, Chief of OSA’s Scientific Communications Branch, for the Web site, www.thecoolspot.org, that was judged outstanding for its effective and simple communications.
  
  
• Dr. Norman Salem, Chief of the Laboratory of Membrane Biochemistry and Biophysics, received the Supelco/Nicholas Pelick Research Award from the American Oil Chemists' Society at its 93rd annual meeting in May for outstanding original research pertaining to fats, oils, lipid chemistry, and biochemistry.

Dr. Bridget Grant, Chief of the Biometry Branch in the Division of Biometry and Epidemiology, described NIAAA's latest survey, the National Epidemiology Survey on Alcohol and Related Conditions (NESARC). The 43,095 survey respondents comprise a nationally representative sample of U.S. residents, aged 18-years and over, including persons living in Alaska, Hawaii, and in non-institutional group quarters.

The first wave of NESARC went to the field in September 2001 and ended in late May 2002. All interviews were conducted in person by workers for the U.S. Census Bureau under the direction of NIAAA. Preliminary analyses indicate that the Survey’s response rate was about 85.5 percent—a remarkable accomplishment at a time when non-response is a growing problem.

The sampling frame for NESARC, the Census Long-Form Transitional Database (CLFTD), was compiled during 2000 and 2001 when 78,300 households per month were being interviewed and included 2,000 primary sampling units (PSUs) representing all 3,142 counties or county equivalents in the United States. By drawing two PSUs from each stratum of the CLFTD database, the NESARC sample totaled 613 PSUs. In the final data tape, these will be reduced to 430 to avoid any potential for inadvertently identifying respondents in the smaller PSUs.

Importantly, information about race and ethnicity that was collected for the CLFTD allowed NIAAA to oversample African Americans and Hispanics for the NESARC. A computer-generated program also oversampled young adults at the household level. A separate group quarters subsample that was combined with the household sample was drawn from the most current Census 2000 group quarters inventory of civilians in non-institutional settings, including boarding houses, campus dormitories, hotels, and homeless shelters, but not jails or prisons. Essentially, the group quarters were converted into housing unit equivalents and sampled along with the households.

Since the same alcohol and drug use, abuse, and dependence variables used in the NESARC survey were also used in a collaborative NIAAA and Department of Justice conducted survey of national jails and prisons that took place at the same time as the NESARC, the results will be an excellent comparative data set.

Because epidemiologic surveys are very costly relative to other research, the NESARC has multiple purposes. It is the largest and most detailed longitudinal survey in the field of alcohol, drugs, or mental health, with a second wave going to the field in 2004 and 2005. All initial respondents will be interviewed again in order to estimate the incidence, as well as the prevalence, of alcohol use disorders and associated disabilities. Second wave NESARC data will also be used to examine factors that impact remission chronicity and stability of alcohol use disorders. Other major interests are estimating the U.S. treatment gap in both alcohol and drug treatment services, determining the characteristics and reasons why persons who need treatment are not receiving it, and assessing the economic impact of alcohol use disorders on work place productivity. Attempts will be made to determine boundaries between safe and hazardous drinking and to understand the magnitude and extent of alcohol use that results in alcohol use disorders. Analyses will target not only college students but also all college-age youth. Finally, NESARC was designed to monitor many of the goals for Healthy People 2010 and the demand reductions targets of the Office of National Drug Control Policy (ONDCP).

A total of 2,000 NESARC interviewers conducted the initial survey. This large number of workers was fortuitous because the New York field office, which was located several blocks from the World Trade Center, was destroyed in the 9-11 attacks. Extra interviewers from the Philadelphia and Boston regional offices completed the survey in NYC. The interviewers hired for NESARC had an average of six years experience. All completed a twoweek training course that was standardized across the 12 Census Bureau regional offices and consisted of one week home study and one week of classes. The interviewers learned the purposes of the survey, the rationale for each section of the interview and how to administer it, how to randomly select one person per household, how to overcome problems with reluctant respondents, and how to differentiate alcoholic beverages as well as multiple drug categories.

A computer-assisted personal interview (CAPI) process facilitated survey administration, assuring that all questions were asked, skipping questions which were answered in earlier responses, and customizing questions for each respondent. The CAPI also disallowed illogical or out-of-range answers and, most importantly, eliminated data entry errors by directly producing machine-readable data. Council members received a paper version of the survey questionnaire.

One major component of NESARC is the fourth edition of the Alcohol Use Disorders and Associated Disabilities Interview Schedule (AUDADIS-IV), an instrument that has been under development for 16 years. A previous version was used in the 1992 National Longitudinal Alcohol Epidemiology Study (NLAES). The reliability of the AUDADIS was assessed by conducting test-retest field studies four weeks apart and ascertaining the concordance of responses. Additionally, one or two sections of 2,500 NESARC interviews were re-administered, as a quality check, to respondents selected from each regional office. AUDADIS demonstrated high reliability for alcohol consumption measures and for alcohol and drug use disorder diagnoses. Actually, the measures yield not only DSM-IV diagnoses for alcohol abuse and dependence, but scales of involvement—a dimensionality matrix—that will be very useful to genetic researchers who complain that dichotomous diagnoses are not informative regarding phenotypes.

To assess the instrument’s validity, NIAAA conducted three clinical reappraisal studies in general populations (i.e., in the United States, Romania, Nigeria) that compared AUDADIS results with clinical interviews. At least 25 peer-reviewed journal articles report the high validity of AUDADIS measures tested by construct validation, factor analysis, and other techniques.

Dr. Grant described many of the major measures in NESARC, noting particularly the race classification categories imposed by the Office of Management and Budget Directive 15 requiring all Federal data collection activities to use the same designations (e.g., Alaska Native, not Eskimo and Aleut). Although the category "other race" has been eliminated, respondents can select multiple categories, which complicates analyses. While the Census is only reporting information for the single categories of Whites, Blacks, Asians, and Hispanic—not for racial mixtures—NIAAA intends to scrutinize the mixed race category in NESARC before determining whether to report findings for any of the larger mixed-race groups.

NESARC includes a very extensive set of alcohol consumption measures that specify beverage-specific information about wine, liquor, beer, and coolers, as well as the usual and heaviest quantity and frequency consumed for each beverage and the time, place, and context of drinking. Photo cards showing different types of glasses help respondents estimate consumption patterns more accurately. Other measures look at age of drinking onset and alcohol abuse or dependence. One innovation adds withdrawal measures that help determine dependence criteria for diagnoses, but also assess the severity of the withdrawal syndrome. Information pertaining to mental disorders and alcohol abuse/dependence is collected for two timeframes: past year and prior to the past year—not for lifetime diagnoses.

For the first time, the survey is attempting to determine whether mood and anxiety disorders are substance-induced, related to a physical illness, or represent underlying states—true diagnoses— that do not dissipate with abstinence or medical treatment. Once substance-induced depressions are ruled out, for example, it may turn out that extensive comorbidity between alcohol and drug use disorders and other mental disorders doesn't exist.

Information is also collected on tobacco use—for cigarettes, cigars, pipes, snuff, and chewing tobacco. For each, questions are asked about age at first use, last use, and daily use as well as the quantity, frequency and duration of use. There are measures of tobacco dependence and withdrawal and similar information regarding onset recency, number of episodes, and remission.

Drug-specific information is collected separately regarding use of many classes of psychoactive drugs, as well as drug-specific diagnoses of abuse and dependence. Questions address the utilization of 13 types of alcohol and drug treatment as well as reasons for not seeking treatment.

Information on psychiatric disorders is classified according to DSM-IV-TR terminology. Family histories determine alcoholism, drug abuse, antisocial personality, and major depression among first, second, and third degree relatives. Other NESARC measures include medical conditions related to alcohol, recent stressful life events, gambling problems and pathological gambling diagnoses, frequency and duration of hospital stays, crime victimization, and pregnancy during the past 12 months and its relation to drinking.

Discussion: In response to questions and comments from Council members and the audience, Dr. Grant clarified that:

• NIAAA hopes to collect DNA samples and other biological materials in conjunction with the second wave of NESARC to facilitate later genetic analyses.
• The average time needed to conduct an interview was 70 minutes during the first month of the survey that dropped to an OMB-acceptable 50 minute average within 6-weeks.
• The survey collects information on marital status, but not sexual orientation. When a question about sexual orientation was suggested for the National Household Survey on Drug Abuse (NHSDA), investigators feared that the question’s sensitivity would lower the response rate from its current 72 -73 percent. However, the NHANES does have an item on sexual orientation, which is administered with an audio CASI that allows respondents to answer in complete privacy by simply pushing the screen. Many large studies address sexual orientation because of its association with differences in substance use/abuse patterns and the prevalence of a number of other conditions.
• The questionnaire, data set, and documentation for the survey will be available on the Web. Clean data sets for NIH surveys are usually released between 12- and 18-months after field data collection ends, with the timing reflecting the complexity of the survey and whether it’s a an initial or continuing effort. Extensive imputation will be completed to assist data users with multivariate analyses for age, race, ethnicity, and so forth. Diagnoses will also be released along with the data tape.
• The NESARC sample includes military personnel who live off military bases, but not those living in military installations, even though these are most likely young adults, aged 18 to 24 years—a target population of great interest.
• Analyses of NESARC will include cross-sectional comparisons with data on alcohol abuse and dependence, drug abuse and dependence, and depression that were collected in 1992 to look at changes over the decade. This is the first time that longitudinal data spanning a decade of alcohol abuse and dependence diagnoses are available.
• The data do contain a State identifier, but the sample will not be representative at the State level. This would have required a sample of 600,000 to 700,000 respondents—too massive for serious consideration. While the NHSDA does have a larger sample, with 800 to 900 respondents per State, accurate State-level estimates for drug use and disorders have been difficult to derive—partially because drug use is less prevalent than drinking and some alcohol problems.
• With respect to collecting useful information on disabilities, NESARC does have diagnostic measures of impairment and some independent measures of disability that are not disease-specific. The SF-12 was included because it is independent.
• Information about the use of Brief Interventions as treatment options will be collected as part of NESARC’s second wave.

Action Item: Dr. Caetano suggested that, in view of NESARC’s importance, it might be useful to form an advisory group of investigators from the extramural research community with special interests in priorities for the planned analyses and further development or modification of the survey and interview questionnaire for future waves. This type of external advisory committee would help bridge any gaps between researchers conducting related studies and assigned NIAAA staff and provide a forum for offering cogent suggestions. Dr. Kington readily agreed to consider the idea.

J. Scott Tonigan, Ph.D., Research Associate Professor at the University of New Mexico and Senior Methodologist at the Center for Alcoholism, Substance Abuse, and Addictions (CASAA) in Albuquerque, NM—a major study site for Project MATCH—outlined racial/ethnicity-related aspects of that effort after stating briefly the study’s design and the sample’s ethnic composition.

A total of 1,726 client recruits for Project MATCH were randomized to one of three 12-week treatments: cognitive behavioral therapy (CBT), 12-step facilitation (TSF), and motivational enhancement therapy (MET). Follow-up was at the end of treatment (3-months) and at 3-month intervals until one year post-treatment. About 95 percent of participants were diagnosed as alcohol dependent. The study had five outpatient and five aftercare sites. Clients in the outpatient sites, but not the aftercare arm, were also followed at three and 10 years post-treatment. This long-term follow up is just being completed for the Albuquerque participants who represent about 80 percent of the Hispanic clients in the trial.

The extensive intake assessment battery for Project MATCH consisted of four modules that required eight hours to complete. The most comprehensive follow-up assessments were completed at three, nine, and 15 months post intake. Self-reports were verified with urine and blood samples at three and 15 months, and collateral reports were collected at all follow-ups except one-year. Excellent convergent validity was found between toxicology studies and self-reports.

For purposes of this presentation, the major instruments were a Quick Screen that determined project eligibility and asked respondents to categorize their own race/ethnicity; the Drinker Inventory of Negative Consequences (DrInC), a 50-item catalogue of adverse drinking effects; and the Form 90, a retrospective, 90-day record of daily drinking from which the primary drinking measures—percent days abstinent (PDA) and drinks per drinking day (DDD)—could be calculated. Two process measures were also collected: the Working Alliance Inventory was assessed after two weeks of therapy, and the global Satisfaction with Treatment was evaluated at termination.

To prevent bias, equal proportions of Hispanic, African American, and White clients were randomized to the three intervention groups. Nonetheless, ethnic-related conclusions about Project MATCH can only be suggestive, not definitive, since only small percentages of clients were from minority groups. In the combined samples, 80 percent of the subjects were Caucasian, 10 percent were African-American, eight percent Hispanic, and two percent other—usually Asian or Pacific Islander. African-American clients were under-represented in the outpatient arm and modestly over-represented in the aftercare sample. Hispanic clients were over-represented, but not significantly, in the aftercare sites, while female African-American clients were significantly over-represented in the outpatient arm.

With respect to pre-treatment characteristics, African-American and Hispanic clients drank about as frequently and with about equal intensity in the 90 days before intake. Relative to Caucasians, African-Americans in both outpatient and aftercare samples reported significantly higher religiosity, higher cognitive impairment, and less readiness to change drinking behavior. Relative to Caucasians, Hispanics also reported significantly higher religiosity, but no differences in cognitive impairment or motivation for change. Further, Hispanic clients were generally younger and had fewer years education than African-Americans or Caucasians.

During treatment, African American and Hispanic clients attended all forms of therapy significantly less often than Caucasians—missing about one more session. At the outpatient sites, African Americans and Caucasians had similar attendance patterns, but Hispanics attended consistently less often. Attendance patterns in the aftercare sites were the reverse, with African American clients attending proportionally less therapy than Caucasians.

To ascertain reasons for this difference in attendance patterns, three variables from the Working Alliance Inventory were examined. Ethnicity was not found to influence either bonding with the therapist (e.g., feelings of trust or willingness to be open) or acceptance of therapeutic goals (e.g., total abstinence). Significant differences, however, were found among the ethnic groups with respect to accepting the therapeutic tasks involved in the three interventions. In general, Whites agreed less with therapeutic tasks than Hispanics or African Americans, and they were notably less supportive of the 12-step approach than counterpart Hispanic or African American clients. By contrast, Hispanic and African American clients were significantly less satisfied with therapy than the Caucasian clients.

Unexpectedly, based on differences in pretreatment characteristics and treatment responses, no differences by ethnic group were found in post-treatment outcomes when aftercare and outpatient samples were combined. All three groups increased their abstinent days dramatically during treatment and sustained a pattern of reduced drinking—at about 70 to 80 monthly PDA—across the year following treatment. However, significant differences emerged in ethnic-related treatment response by sample type, with African Americans reporting significantly higher abstinence rates than Hispanics and Whites in the outpatient, but not the aftercare, arm. Even though African American women were over-represented in the outpatient sample, gender was not found to impact African American clients’ significantly more positive treatment outcomes relative to Hispanics and Caucasians.

Additionally, analyses of drinking intensity—number of drinks per drinking day—found no differences among the three ethnic groups in either study sample across the one-year follow up period. However, Hispanic clients generally drank more than African American or Caucasian clients on the days they drank. While a greater intensity of drinking is historically predictive of negative consequences, these Hispanic clients, when asked to attribute adverse effects to their drinking, denied the connection and thereby revealed what may be an important cultural difference in drinking styles and expectations.

The major finding at the10-year follow up—only for the 122 clients recruited in Albuquerque— is the absence of any difference between Hispanics and Caucasians in PDAs across this entire period. The average Project MATCH subject maintained a 34 percent improvement rate over the intake assessment after 10 years. Also, no evidence emerged that ethnic treatment matching in either aftercare or outpatient samples effected outcomes measured by monthly PDAs or DDDs.

One caveat, however, applies. A somewhat counterintuitive match emerged when CBT and MET conditions were combined and contrasted with TSF for the outpatient sample. While Hispanic clients responded similarly to TSF or the combined MET/CBT conditions, Whites assigned to the 12-Step condition reported significantly higher abstinence rates and significantly fewer drinks per drinking day. This is surprising because Hispanics who reported significantly higher religiosity at intake were predicted to prefer TSF over either MET or CBT.

To explain this unexpected response, ethnic matches in the client-therapist dyads were examined. Surprisingly, Hispanic and African American clients who worked with therapists of a different ethnicity than their own (mismatched) actually fared better than those in matched dyads, although the differences were not significant, the clients were not randomly assigned to therapists, and White clients were not part of the analysis.

In sum, ethnic-related treatment matching seems to be very complex and counterintuitive, requiring more study through a randomized clinical trial. In spite of lower attendance rates and less expressed satisfaction with treatment, Hispanic and African American clients were more accepting than Whites of the assigned therapeutic tasks in all three treatment conditions. This would seem to reflect a lack of knowledge about clients’ expectations of formal treatment and their therapists’ roles in recovery. More also needs to be known about how clients from different cultures perceive the relationship between drinking and consequences. The absence of discernable ethnic differences in post-treatment outcomes, despite observed differences in negative prognostic indicators, also suggests that more needs to be learned about what resources in addition to formal treatment individuals mobilize to support positive behavioral change (e.g., AA attendance, community programs).

Discussion: In the discussion with Council members, Dr. Tonigan agreed that future analyses of the Project MATCH data might fruitfully examine:

• Whether socioeconomic status—measured by annual income and/or the Hollingshead vocational scale—impacts response to the three treatment conditions.

• Whether other variables such as comorbidity are strongly associated with ethnicity, as well as socioeconomic status, and predict poorer outcomes or exclusion from the study. A lack of health insurance coverage was previously found to be a proxy for lower socio-economic status and also, to a large extent, for Hispanic and African-American ethnicity.

• Whether assumptions regarding the positive impact of religiosity among the Hispanic and the African American populations on response to TSF are faulty because members of Pentecostal or Baptist congregations do not find AA congruent with their beliefs

• Whether frequency of church attendance is associated with more—or less—attendance at TSF and other conditions and how this aligns with post-treatment outcomes since church participation might compensate for—as well as conflict with—therapy attendance/benefit.

• Whether selection biases inherent in the eligibility criteria for Project MATCH— which excluded persons without a 6^th grade reading ability, without access to treatment or insurance coverage, with less severe symptoms, or who were unwilling to be randomized to treatment—homogenized the ethnic sample and reduced the findings’ generalizability. Differences among applicants with the same self-reported ethnicity who were— and were not—willing to participate in the research might shed light on self-selection biases.

Dr. Hingson also clarified that previous analyses did not find any differential effects on treatment-related outcomes attributable to having a high proportion of persons with the same self-reported race/ethnicity in treatment groups or conditions. By contrast, involvement in the criminal justice system (e.g., court-mandated treatment, pending convictions) was associated with ethnicity and did impact participation. In Albuquerque, a higher proportion of Hispanic clients than Whites had some legal involvement.

Dr. Lorraine Gunzerath from the Planning and Evaluation Branch of the Office of Scientific Affairs reported on the three-day NIAAA-sponsored Workshop on Alcohol-Related Gene-Environment Interactions, designed to help formulate plans for future research in this area.

As background, Dr. Gunzerath explained that an individual’s vulnerability alcoholism stems from both genetic variations and environmental circumstances. Reliable identification of the sources of liability variation, as well as quantification of liability, would help target at-risk individuals for preventive interventions before alcohol use, abuse, or dependence phenotypes emerge and also facilitate the design of prevention programs addressing a combination of genetic and environmental vulnerabilities—not as isolated components.

A substantial amount is already known about how both contemporaneous and historical environmental factors influence alcohol consumption. By using animal models to map genetic influences, intermediate phenotypes have been discovered, the search for alcohol-related chromosomal regions has been narrowed, and the possibility has been raised that different genes in males and females influence alcoholism onset. Human studies have identified two protective genetic variants: aldehyde dehydrogenase and alcohol dehydrogenase. Several chromosomal regions likely to contain additional alcoholism-associated genes have also been identified.

Despite progress in these separate fields, few studies of gene-environment interactions have been conducted, largely due to design difficulties and the cost of longitudinal efforts. Thus, one specific goal in NIAAA’s Strategic Plan for 2001-2005 is to advance knowledge about the influence of environment on expression of genes involved in alcohol-associated behavior, particularly among vulnerable adolescents and other special populations.

The Workshop included presentations on the current state of knowledge in this area, as well as barriers and opportunities for targeted research. A series of break-out panels that focused on various research-related problems in gene-environment interaction studies were charged with explicating specific issues and generating relevant recommendations. The following agreements were reached:

Issue One: The dearth of identified alcohol-related genes and the potential prematurity of interaction studies unless/until they are conducted in the context of specific genes.

The three recommendations to address this issue were:

• Continue and expand support for using animal models that are valuable components of genetic research on alcohol-related phenotypes. Such gene mapping strategies may identify candidate genes and polymorphisms that have direct counterparts in human species or have functional implications for the same critical neurobiological systems. In contrast to human research, features of both the genetic makeup and the environment can be controlled and manipulated in animal models to assess gene expression at various developmental stages and to study an entire life span within a relatively short time frame.

• Foster NIAAA participation in trans-institute genomics research at NIH. A large-scale, genome-wide case-control association study is needed to identify genes relevant to alcoholism and many other behavioral disorders and should focus on severe, clear-cut cases of alcoholism and the end-states of other diseases.

• Initiate gene-environment interaction investigations that use plausible alcohol-related genes or intermediate phenotypes in the absence of definitively established genes. The complexity of influential variables in gene-environment interactions may impede the identification of relevant genes in purely genetic studies since candidate genes with inconsistent or weak support may only manifest effects in interaction with specific environmental factors. It is possible that a gene with a real effect in the presence of one dimension of an environmental factor has no effect—or the opposite effect—in the presence of some other dimension of that factor. Without specifically measuring or controlling for environmental aspects, the studied sample may include subjects whose outcomes offset each other, despite genetic concordance, and yield inconclusive results.

Issue Two: Inconsistent definitions and phenotype measures across studies impede comparisons of genetic or environmental results and combinations of existing data sets to provide adequate sample size and power.

The two relevant recommendations were:

Standardize assessment methodologies by using phenotypes derived from laboratory-based objective measures, not symptom tallies. Diagnostic criteria for the alcohol use, abuse, and dependence phenotypes have been plagued by marked overlaps in symptom clusters that are a common indicator of a continuously distributed variable. Limitations in self- and collateral reports underscore the need for a standardized methodology for assessing the phenotype which would also facilitate data pooling and replication efforts.

• Use intermediate phenotypes instead of the traditional dichotomous clinical diagnoses of alcoholic/nonalcoholic for gene-environment interaction studies. The best prospects for alcoholism-associated intermediate phenotypes appear to be a flushing acetylaldehyde response, an alcohol benzodiazepine response, impulsivity, antisocial personality disorder, brain wave measures, and measures of executive function and cognition.

Issue Three: Genetically-influenced sensitivities to environmental factors typically apply to specific environmental risks, and, since the relevant alleles often appear in only segments of the population, most studies do not have sufficient power to detect such interactions.

The two recommendations to address this issue were:

• Encourage trans-institute NIH studies or NIAAA-sponsored multi-institutional investigations with sufficiently large samples and statistical power to detect interactions among specific genetic loci, behavioral characteristics, and environmental risk factors and/or moderators. A trans-NIH institute initiative could examine dependencies on nicotine, alcohol, and illicit drugs and look at such behavioral or mental health outcomes as attention deficit disorder, depression, or anxiety. A multi-site collaboration could focus on such environmental risks as early trauma, poverty, or disruptive home settings that are associated with many different disorders. While particular effects may depend on the specific genetic vulnerabilities of the exposed individual, a family study could help separate the effects of specific risks.

• Focus on especially informative groups and individuals. Special populations offer many research advantages, including prevalence of a particular genetic variant or saturation in a particular cultural environment. Exceptionally informative populations include twins, families with siblings, isolated groups with easily accessible, extended families, and groups with extensive historical registries and records. Inter-generational gene-environment interaction studies of families with alcoholic parents might be especially fruitful. Outliers—or individuals whose actual level of alcohol use or abuse conflicts with expectations derived from their liability profile—are another interesting population, whether these individuals carry protective genes but manifest alcohol abuse or do not develop the negative outcome despite multiple documented risks.

Issue Four: Unresolved methodological and statistical issues hamper efforts to measure the environment and to disentangle the effects of multiple correlated factors.

The two recommendations in this area were:

• Develop multi-disciplinary investigator teams that use innovative, prospective research designs for gene-environment interaction studies that incorporate multi-perspective, longitudinal, and genetically informative data. Collaborations among investigators experienced in human development and sociological research should be fostered. Since a lengthy developmental process is needed to produce an individual phenotype, studies of sufficient duration are needed to examine the transition from use to abuse to dependence and, where possible, reversal and relapse. Appropriate peer review mechanisms must be established that do not penalize such long-term, multi-disciplinary studies.

• Identify tools for disentangling environmental risk factors from each other and from genetic variance. The large, multivariate, and complex databases needed to study the interplay of genetic and environmental risk factors may require the application of such suitable statistical techniques as nonlinear growth curves. Also, a standardized methodology is needed for assessing major environmental risk factors and tying specific risk factors to specific alcohol-related mechanisms. Although most studies or interaction effects assume that the variables under consideration act independently, many of the presumably environmental factors have a heritable component, such as personality traits, that reflect an individual's genetically influenced characteristics.

Council member, Dr. Raul Caetano, reported on the discussions of a Workshop panel that deliberated research issues affecting gene-environment interaction studies of special populations and defined these groups as having unique characteristics with respect to either their alcohol-related genomes or environmental configurations.

A number of important ethical concerns were identified, including feelings among members of these special populations that researchers overuse them. Investigators working with these groups should be very aware of, and respect, their cultures and institute formal, sensitive, and clearly-explained informed consent procedures. Care needs to be taken to avoid recruitment bias and stigmatizing individuals in small population groups—especially if mainstream society judges a prevalent behavior as "deviant." Adequate human subject protection safeguards for these groups may require multiple IRBs that reflect the ethical standards of both the medical and the special community.

The reasons for studying these special populations include the existence of a particular polymorphism such as ADH2, access to carefully-collected registries and records, a need to validate cross-cultural findings, either high or low saturation (exposure) for a particular environmental risk, an identifiable health-related need, and natural experiment opportunities to contrast different populations in different environments.

Measurement issues are particularly problematic in special population studies, not only because it is difficult to recruit large samples of minority group subjects, but also because any research hypotheses reflecting three-way interactions between gene, environment, and ethnic group require considerable power to test.

Professional training is another issue because many researchers in the alcohol field are not experienced in working with minority groups, and well-trained researchers from minority groups are in short supply.

Unfortunately, researchers in the alcoholism field are fragmented and too seldom collaborate in cross-disciplinary studies or agree on common measures and terminology. This is particularly troublesome when looking at interactions between such two isolated and disparate fields as genome and environment. One recommendation for NIAAA to consider is organizing a series of consensus conferences to address cross-disciplinary issues in measuring the phenotypes and endophenotypes of interest.

Discussion: In the ensuing discussion period, Council members reiterated several points.

Gene-environment interaction studies cannot be simple two-way efforts, but must be very large, complex, and appropriately powered n-by-n dimensional investigations that factor in many different genes with many different environments and all the interactions among them.

Several efforts are already underway to conduct very large population studies that still may not be adequate for examining all these complex issues. One of the largest is the child cohort study led by NICHD that will follow the gene expression and environmental exposure of 100,000 prenatally-identified children as they mature. Similar efforts are underway in England to recruit a sample of 500,000 from the National Health Service.

It may be possible to drop ethnicity as a separate variable in very large gene-environment interaction studies if the analyses reveal representative clusters/variants of gene-environment variables that could serve as substitutes. That assumes that ethnicity can be appropriately decomposed into a combination of gene and environment—a large challenge.

Referring to documents in Council members’ folders, Dr. Warren explained several procedural matters pertaining to Council functions and the grant award process.

According to NIH rules, the Operating Procedures for Institute Staff Actions for Administrative Supplements and Time Extensions, which were last updated and approved by Council in February 2001, must be reconsidered. The document’s first two pages basically delegate authority to the Institute for making specific time and budget extensions, budget increases, and administrative supplements when various exigencies arise such as loss of equipment, increased research costs, and other serendipitous opportunities requiring immediate action. Under current parameters, administrative supplements for up to $50,000 per year in direct costs can be approved by a Director of any NIAAA Division or Office. Increases in the range between $50,000 and $100,000 also require sign-off by the Institute Director and a report to the Advisory Council. Many of the requested supplements are for reentry into research through the under-represented minority investigator program, typically for women who leave temporarily to assume familial responsibilities.

After both Drs. Warren and Kington recommended retaining the current parameters that require Council consideration and approval of supplementary budget requests exceeding $100,000. A motion to approve these proposed operating procedures was seconded and unanimously accepted.

Following the relatively recent introduction of formal procedures at NIH for expediting en bloc concurrence of grant applications, the NIAAA Council adopted the process two years ago and increased the threshold levels last year. The purpose of this effort is to accelerate Council consideration of grants with the best priority scores and most meritorious rankings that are not from foreign countries and do not have any bars to awards such as human subject, gender, or minority representation concerns. Since grant applications that meet these criteria are seldom discussed in closed Council sessions, a mechanism for expediting their approval is appropriate.

To implement this procedure, the Chair of the Advisory Council designates a single Council member to act on behalf of the entire body in reviewing summary statements for qualifying applications with a specific program class code and making a concurrence recommendation. At the same time that a Council member is asked to assume this responsibility, all other Council members are notified too so they can look at the applications, even though the summary statements are already available on the electronic Council book. During the following 2-week window, any Council member may indicate a desire to have any grant application considered by the full Council—whether or not it falls into the program class code a designated Council member has been asked to review and recommend for expedited concurrence.

When this program was initiated, NIAAA specified that applications in this expedited category must have a cutoff percentile score of 20 or better (or a cutoff priority score of 200 or better for applications without a percentile score) and a maximum allowable direct cost of $350,000. Last year Council increased the cost threshold to $500,000 because clinical and epidemiological applications tend to have higher costs and were more frequently excluded from consideration than other program class codes.

According to Dr. Warren, the expediting system has worked well and was applied to between 31 and 37 applications in each round last year. While many awards are still not made before Council meets, the process does begin earlier and investigators do receive an expedited award. Almost all the funding mechanisms are included in this procedure except P applications and cooperative agreements which must be brought to the Council’s direct attention.

To answer a question about the potential impact of future budget cuts on this procedure and whether the 20 percentile cutoff level would be maintained, Dr. Warren clarified that the criteria applied to expedited Council review, was not necessarily awards. Currently, NIAAA’s pay line is about the 20 percentile. Dr. Kington added that the Institute is considering various options to lessen the impact of an anticipated leveling-off in funding, but Council can always choose not to exercise the expedited concurrence procedures. Also, Council can change the qualifying parameters at any meeting, but they must be approved at least once a year. If approved now, Council will have to reconsider these procedures no later than next June, although they can be brought up again at any time.

To a query about whether the procedures have successfully expedited awards, Dr. Warren explained that the mechanism has not been as helpful as hoped in making awards before the Council meetings, but they are going out shortly thereafter. Once NIAAA receives a Council concurrence recommendation, the rather lengthy award process can begin. The procedure also reduces the staff burden, smoothes their work, and makes them more available to work directly with Principle Investigators.

A motion to continue the present procedures for expediting approval of qualifying grant applications was made, seconded, and accepted by a unanimous show of hands.

After Dr. Warren asked whether changes were needed in the minutes of the February 6-7, 2002 Council meeting, a motion to approve them was seconded and unanimously accepted without further discussion.

Continuing the traditional presentation by a Council member, Sandra Brown, Ph.D., Professor of Psychology and Psychiatry at the University of California, San Diego, shared her outcome findings for several adolescent cohorts that were followed for extended periods following treatment for alcohol and drug problems. Dr. Brown began by noting how little is known about the drinking patterns of youth other than when they initiate and escalate alcohol and other drug consumption and what risk and protective factors contribute to use decisions. Few studies have addressed adolescents’ fluctuating involvement and de-escalation efforts as they move through alcohol careers or the impact on outcomes of highly-charged developmental changes in their social, emotional, biological, and cognitive dimensions. Crucial changes in the prefrontal cortex and hippocampus that occur during the time when youth typically begin drinking or having problems with alcohol help explain teens’ impulsivity and faulty decision-making capabilities.

The first cohort of 166 adolescents for which Dr. Brown reported treatment outcome results entered a long-term study on admission to one of five participating inpatient treatment programs when they were 14 to 18 years old. These patients were initially assessed after several weeks of abstinence and then followed at 6-months and annual intervals thereafter until approximately 30-years of age. The 10-year follow-ups are underway. Nearly two-thirds of the youth are male and the majority are Caucasian from a range of socioeconomic backgrounds in California. All were diagnosed as alcohol dependent and most had used other substances in addition to alcohol and met criteria for at least one other specific substance use disorder. None had any corroborated psychopathology except conduct disorder that predated onset of alcohol dependence.

As seems to be true in most studies comparing adolescent and adult treatment outcomes, the proportion of these youth who maintained improvements for the first post-treatment year was roughly comparable to abstention rates for adults in Project MATCH. This is somewhat disappointing because adolescents have generally not been drinking as long as adults, although developmentally, they have less refined cognitive and behavioral coping skills. However, the proportion of youth who seem to have minor lapses rather than full-blown relapses in this first post-treatment year is much larger than for adults.

By the 4-year post-treatment follow up, different patterns of substance involvement began to emerge. Nearly half of the young subjects were labeled non-responders who were using substances heavily and having problems even though they had done well for the first two years after discharge. Another quarter of these adolescents were substantially improved four years after treatment. While only a small proportion (seven percent) remained totally abstinent from all substances except cigarettes the entire time, the rest only used alcohol or marijuana infrequently and reported no related problems. About 10 percent of this sample had a major relapse in the first 6-months after treatment, but quickly stabilized and continued to do well.

Among the group that were using heavily four years after treatment, the prevalence of alcohol, nicotine, marijuana, stimulant, and other drug use was two-and-a-half times greater than national prevalence rates measured by the National Household Survey. The intensity of drinking had also returned to that at treatment entry when all met criteria for alcohol dependence.

When adult and adolescent relapse patterns are compared on Marlatt and Gordon’s cognitive behavioral model, adults appear to relapse in situations where they experience negative affect (e.g., anxiety, irritation, anger, conflict, depression), while most youth report being in a good mood, but in an unsupervised social setting with other peers. Their neurocognitive development level also influences how youth respond to high-risk situations. Only half of adolescents seem to anticipate that they're going to have a difficult time in a relapse situation, and they consistently underestimate the potential impact of substance use triggers/cues. Additionally, youth generally enjoy using drugs, but want to avoid problems: the predominant motivation in averting relapse is elimination of alcohol- or drug-related problems, not abstinence. The environmental constraints affecting youth are also quite different from those to which adults are exposed.

Although investigators are learning why teens fail after treatment, less is known about factors contributing to success. Participation in self-help groups such as AA and NA seems to benefit adolescents as well as adults. Those who attend regularly do, apparently, sustain a motivation for abstinence, which is the best predictor of continued success. Unfortunately, less than half of the youth studied regularly attended 12-step meetings, and a major deterrent for them was the focus on abstinence. However, convenience of the meeting location and the presence of other friends or same-age peers in the group were salient predictors of attendance.

In addition to attendance at 12-step meeting, youth took two other primary pathways to success. One entailed reintegration of younger teens into a supportive family that created some structure in their lives. Older adolescents who stop drinking and drug use were more likely to stay away from dysfunctional families with an extensive history of alcoholism and drug abuse, but to attend school, work, or other volunteer activities full-time. Youngsters who remain abstinent following treatment also tended to live in expressive families that communicated about both positive and negative aspects of family functioning. Other functional dimensions associated with better— or worse—treatment outcomes include sexual risk taking behavior, health problems, accidents or injuries, and doctor or emergency room visits.

Another study, Dr. Brown reported, examined the impact of alcohol treatment on neurocognitive functioning in youth, aged 15 to 17 years, who had used alcohol a minimum 100 times, but had no confirmed head trauma, neurological illnesses, Axis I psychiatric disorders, recent substance abuse, or dependence on other drugs. These subjects, who were administered a neurocognitive test battery after 3-weeks of abstinence, retained verbal or non-verbal information they had learned about 10 percent less well than a non-drinking comparison group. Subjects’ visuo-spacial memory capabilities, which remained stable as long as they maintained post-treatment improvements, deteriorated if they resumed drinking. Any experience of withdrawal symptoms during the 4-year post-treatment period predicted a deterioration in visuo-spatial functioning.

To explore the neuroanatomical basis for these memory problems, the investigators used functional magnetic resonance imaging (fMRI) to observe brain functioning while subjects performed a visuo-spatial memory task. Showing a series of summary slides, Dr. Brown pointed out the composite activation patterns for blood oxygen level-change dynamic (BOLD) responses in given regions in the brain documenting that alcohol-dependent youth with poorer behavioral measures of spatial working memory than normal controls also have different brain activation levels, particularly in the right parietal region. These neuroanatomical studies are helping researchers understand what portions of the brain don’t operate optimally for alcohol-dependent adolescents and how that is linked to memory deficits and associated school difficulties. Three separate studies have now demonstrated that these brain activation patterns, as well as behavioral measures of subjects’ thinking deficits, are linked more closely to whether adolescents have experienced withdrawal symptoms than to how much alcohol they've consumed. Hence, alcohol withdrawal may be an important phenotype for alcohol dependence among youth.

Another important finding from a study of treated youth is that the subset with comorbid alcohol or drug dependence and another Axis I psychiatric disorder have higher rates of relapse and relapse sooner—during the first 6-months post treatment—than youth with only substance-related diagnoses. Moreover, some of the comorbid psychiatric disorders predict poorer outcomes than others. Adolescents with a conduct disorder and/or oppositional defiant disorder have worse outcomes than counterparts with different psychiatric problems. The adolescents within the psychiatric comorbidity group who have the worst outcomes are those with anxiety disorders. By contrast, the youth who have mood disorders do better. This may be because they are medication compliant or receive more treatment following inpatient hospitalizations.

In conclusion, Dr. Brown disclosed that she is clustering individuals with similar characteristics on a given dimension such as alcohol outcomes and using latent class growth analysis techniques to examine outcomes over an eight year period. This approach has yielded four major alcohol use trajectories. First, approximately 18 percent of youth continue to drink heavily during the initial 6-months post-treatment and sustain this pattern at least through age 25 years. At the other end of the continuum, nearly 22 percent of the sample is almost always abstinent and problem-free. A third group of about 25 percent uses alcohol in moderation at a relatively stable, infrequent rate and with few problems. The fourth cohort, consisting of about a third of the sample, worsens substantially after the 4-year post treatment point even though they appeared to be moderate, trouble-free drinkers until they reached 18 ½ to 21 years of age. Moving away from the home-of-origin environment seems to be a critical period of development and a high-risk point for some young adults to start using more alcohol and other drugs. Substantial differences in functioning are also associated with these four major trajectories. For example, youth who remain abstinent after treatment are four times more likely to be in college than youth who resume drinking.

Discussion: During the discussion period, Dr. Brown and Council members made several interesting points.

Increasingly, data from animal models show that intermittent exposure to alcohol produces more toxicity and more negative motivational effects than stable drinking patterns. Animals that are intermittently exposed to alcohol drink larger quantities and consume it more rapidly than other comparison cohorts. To investigate these findings in youth, Dr. Brown is clustering some variables to more closely approximate binge-drinking episodes.

With respect to long-term outcomes for the four trajectory groups, as yet unpublished data indicate that the youth cohort with the poorest mental health outcomes at 8-years post treatment is not the group with the highest continuous level of use, but the group that got worse over time. Comorbid mental disorders and involvement with other drugs may precipitate this exacerbation.

Although new findings regarding tobacco suggest that 12 year-old youngsters need only two to three weeks of exposure to develop signs of dependency, it is not yet clear how much alcohol exposure is needed to provoke the neurocognitive effects or neuroanatomical changes Dr. Brown is investigating. In conjunction with other researchers, she is identifying characteristics of high- and low-risk groups and following them over time to map changes in their fMRI responses and neurocognitive performance in relationship to naturally occurring rates of alcohol exposure. She anticipates that the threshold for alcohol involvement is lower than previously thought.

As to whether such environmental factors as price effect youth drinking patterns as they mature and become responsible for themselves financially, Dr. Brown noted that the issue is more complicated than simply looking at the transition from being dependent on parents because the youth who actually make the most money are drug dealers.

With regard to patterns in the sequencing of relapses, there's a disproportionate representation of early alcohol and marijuana involvement in initial relapse episodes. However, youth who prefer another substance are more likely to relapse initially with polysubstances. While these adolescents progress to using other substances consequent to alcohol or marijuana use at about the same rates, it’s a more gradual process if they initially use alcohol or marijuana than if they prefer stimulants or other substances. This may have clinical implications. While the natural response is to treat the drug of choice, it may be the drug of least interest that poses the most risk and requires more educational efforts.

Ms. Diane Miller, Chief of the Scientific Communications Branch, introduced the newly released video, Alcohol: A Woman’s Health Issue. The 12-minute video was a collaborative project with the NIH Office of Research on Women's Health. The video features seven women of different ages and ethnic backgrounds who share their alcohol-related experiences from early drinking problems through treatment and recovery. Their narratives are intermixed with comments from NIAAA’s Deputy Director, Dr. Mary Dufour, and from the Director of the Office for Research on Women's Health, Dr. Vivian Pinn. The video was pre-tested with a number of focus groups, which were complimentary about both the content and the style of presentation.

Discussion: Following a showing of the video, Ms. Miller made the following comments in response to questions and suggestions from Council members and other audience participants. The video is ready for release and free copies will be sent to all Council members and representatives of other Advisory Groups. It will also be distributed to treatment centers, EAP projects, and other venues suggested in the focus groups. We will be contacting Lifetime, a cable television network for women, and the Oprah Winfrey Show to see if they would be interested in airing the video or segments of it. It will also be shown at a number of alcohol-related events and conferences. Segments may be repackaged for special audiences, including middle- and high-school students, college freshmen, and business professionals, and girls. Consideration should be given to making a DVD version that would be easier to put on a laptop computer and take to meetings or conferences.

Ordering information will be posted on the NIAAA Web site and in the publications catalog. Interested persons may call the Scientific Communications Branch at 301-443-3860.

Action Item: Dr. Warren asked Council to consider a need to increase the number of minority-serving institutions applying for research grants under the RFA on college-drinking. Dr. Alpha Brown, who initially raised the issue, added that colleges and other institutions of higher learning that serve socioeconomically disadvantaged students, as well as racial minorities, need to be empowered to apply for and be awarded NIAAA-sponsored research grants. The necessary competence to complete the application process successfully is not always present in these institutions, and some form of technical assistance or guidance may be needed. This is not affirmative action, but assistance for any socioeconomically deprived group that may or may not have an over-representation of ethnic or racial minority members.

Dr. Warren concluded that the issue, once formally in the minutes and brought to the attention of the full Council, would be followed up by staff.

Mr. Lee Dixon, Director of the Health Policy Tracking Service at the National Conference of State Legislatures (NCSL) explained the functions of his organization that might be of interest to Council. He began by noting the NCSL has offices in Denver and Washington, D.C., to address the information needs of 7,000 State legislators and their 30,000 staff members regarding political aspects of education, labor, budget, taxation, the environment, and law and justice issues. Four sections within NCSL focus on health. The two in the Denver office deal with maternal and child health issues in conjunction with the Health Resources and Services Administration (HRSA) and with prevention programs, working with CDCP on HIV/AIDS, chronic illness, and child and adolescent health. In the Washington office, the Forum for State Health Leadership helps train new legislators who aspire to leadership positions on health committees.

The Health Policy Tracking Service (HPTS), identifies, analyzes, monitors, and reports on health legislation and policies in all 50 States. In 2001, more than 29,000 health-related bills were introduced in the States and most of them carried over to 2002. HPTS summarized more than 18,000 pieces of legislation last year—all the bills that passed in either a State House or Senate (or Assembly, as some are called).

This legislation is categorized in seven subject areas: HIV/AIDS, tobacco, pharmaceuticals, providers, Medicaid, private healthcare financing, and behavioral health—the subcategory for alcoholism, drug addiction, and mental health. Subcategories within the major subject areas cover over 300 topics. For substance abuse, there are 14 different topics that include prevention, legal issues, and all types of treatment for adults, children and adolescents, infants, women, drug courts, homeless, medication, prisoners, and the TANF program for persons on welfare. Parity issues in insurance coverage are also followed closely as part of the substance abuse category.

All of this legislation is published on the Internet and entered into three different databases for the purpose of keeping State legislators abreast of new information via bi-weekly e-mail alerts. The databases are also marketed to public and private sector organizations and companies. In Legislation to Watch, health care bills that could impact State policy are summarized in an objective, neutral style that specifies what each bill purports and predicts its impact if enacted.

A total of 10 electronic newsletters, Snapshots, are produced bi-weekly to summarize major trends or unique actions in selected areas. On the subject of substance abuse, six topics that 300 key State legislators declared priority interests for the year are routinely covered: emerging issues, parity and insurance coverage, treatment in lieu of incarceration, Medicaid services and eligibility, pharmacotherapy, and alcoholism.

HPTS also produces special Issue Briefs that contain original research on specific interests, typically reporting recent legislative actions, pending laws or bills, and both sides of any arguments. Three Issue Briefs pertaining to alcoholism and addiction treatment services have been published (i.e., parity, California Proposition 36, drug courts) and two more are planned for fall (i.e., pharmacotherapy and treatment of co-occurring addiction and mental illness). Once published, Issue Briefs are updated quarterly.

With funding from CSAT and the Robert Wood Johnson Foundation, the Tracking Service also provides technical assistance to State legislators and their staff on specific topics by sponsoring short presentations or bringing in experts from the field to help develop better programs. A major thrust is educating State legislators that treatment does work. The research conducted by NIAAA is an important aspect of this knowledge development process that helps State legislators make better informed decisions about appropriations—whether for treatment services, training, or research.

Discussion: During the discussion period, Mr. Dixon clarified the following points:

A number of organizations and associations related to substance abuse access the Health Policy Tracking Service databases, including the National Council on Alcoholism and Drug Dependence, Partnership for a Drug Free America, CADCA, Legal Action Center, and the alcohol industry.

State legislatures are much more amenable to change than the Federal Government.

Currently, HPTS does not analyze and track legislation in the States related to drinking and driving (this is currently done by another NCSL group), but does access all the bills. Mr. Dixon would be amenable to making information on this topic that has already been compiled by the National Highway Traffic Safety Administration and Mothers Against Drunk Driving, as well as linkages to the new college drinking Website, available through the HPTS listservs that access 250 legislators and staff nationwide.

Although no legislation is currently moving through in-session State legislatures that aspires to move involuntary treatment for substance use disorders out of the criminal justice system and into the civil commitment system, some previously introduced bills did propose involuntary civil commitment for alcoholism and drug addiction.

With respect to State trends—or proposals—for spending on substance abuse prevention and treatment services, all States are facing large budget shortfalls. HPTS is currently conducting a survey of State appropriation reductions in Medicaid and health programs. It appears that cutbacks for FY 2003 reduced treatment and prevention programs by less than four percent because most States were able draw on "rainy day funds" or savings that accumulated over the past six years of relatively good economic times. However, these are now depleted, and tax refunds increased and tax revenues decreased in all States in April 2002. So, shortfalls will continue through FY 2003. Many State legislatures may have to go into special sessions in the fall to trim their proposed budgets, even though this is an election year.

Dr. Michael Eckardt, Chief of the Planning and Evaluation Branch in OSA, updated Council about recommendations from its Research Priorities Working Group for FY 2004. Although all the Working Group recommendations have already been sent to NIAAA’s Division Directors for their consideration, Dr. Eckardt reviewed those offered by Drs. Caetano, Holder, Samuels, and Triestman.

Dr. Caetano suggested more emphasis on alcohol-related domestic violence; improved treatment for ethnic minorities that addresses both providers’ and patients’ responsibilities; and alcohol-related injuries and trauma.

Dr. Holder was concerned with ways to delay the onset of heavy drinking, noting that the younger minors begin excessive alcohol consumption, the more likely they are to develop alcohol abuse and dependence. Reducing drinking on college campuses is part of this.

Dr. Holder also encouraged the development of objective sensors that could determine continuous levels of alcohol consumption over time, rather than relying on self-reports.

Dr. Samuels expressed an interest in identifying and defining the effective components of treatment interventions as well as school- and community-based prevention activities. More information is needed on the numbers and percentages of people who recover and whether these reflect formal treatment or spontaneous remissions. What are the characteristics of individuals who recover, and what are the costs and social benefits of treatment and prevention?

Additionally, Dr. Steven Treistman, Chairman of the Board of Scientific Counselors that reviews the Intramural Research Program, suggested more attention be given to alcohol and other abused drugs that affect specific receptor systems and may indicate common pathways and mechanisms for addiction. More emphasis is also needed on integrating molecular and behavioral research.

Discussion: After noting the paucity of biomedical suggestions, Dr. Eckardt opened the floor for Council members to make additional suggestions for the Institute’s Division Directors.

Dr. Warren explained that this Research Priorities Working Group normally meets in the spring so that recommendations can be brought to the full Council for further discussion and elaboration before submission to the Institute’s Directors. Because logistical and scheduling problems interfered with a meeting this year, recommendations from individual Working Group members were solicited regarding research priorities of special interest to Council, and this is the first opportunity to share those.

Dr. Deitrich supported the need for more molecular studies, noting the progress in identifying and defining the structure of receptors related to alcohol action. The next step in pharmacogenomics will be to devise small molecules that interfere with, or activate, these receptors, and X-ray crystallography, mass spectrometry, and NMR studies will be increasingly important.

Dr. Edenberg opined that the collection of DNA and other biological samples in conjunction with all large-scale studies would allow NIAAA investigators and other researchers to conduct related pharmacogenomic studies that will ultimately integrate information on the environment, treatment, and biological substrates.

Dr. Hingson reiterated the need for more research on alcohol-related health costs to society, particularly unintentional injuries resulting from the approximately 40 percent of traffic crashes that involve alcohol and are the leading cause of death in the United States for persons aged one to 34 years. Corollary studies are needed on policies and procedures that prevent this mortality and morbidity, including pricing and taxing of alcohol, outlet density, drinking and driving laws, and improved outreach efforts, screening instruments, and treatment interventions for young persons. Renewed attention also needs to be given to comprehensive community interventions that reduce alcohol-related injuries and health problems, particularly among college students. As part of this effort, the testing and reporting systems for persons who die unnatural deaths need improvement. While the United States already has a fatality analysis reporting system that tests blood alcohol levels for about 70 percent of fatally-injured drivers, this needs to be expanded to include not only all fatally-injured drivers but drivers in the majority of alcohol-related crashes who are not fatally injured. More systematic alcohol testing should also extend to other unnatural deaths from homicide, suicide, drowning, burns, falls, and so on. Benchmark data are needed to measure the success of interventions that attempt to reduce alcohol-related mortality. Another variable that needs to be reported in the fatality analysis reporting system is whether or not persons who die unnaturally of alcohol-related causes are college students.

Dr. Koob explained why, as a member of the Working Group, he did not propose any new research priorities. After working exhaustively on the Integrated Neurosciences Initiative for Alcoholism, he hoped more resources would be added to the two clusters already funded and that other related priorities would be continued for the next two to three years. He thought that focusing on too many research areas might diversify the portfolio too much at a time when new genomic and molecular biology interests, as well as rapidly evolving animal models and medications development initiatives, offer a plethora of research priorities for the biomedical field.

Dr. Eckardt clarified that the final research priorities become part of the Congressional justifications (CJs) as areas of emphasis in which new monies would be invested, if available, and are posted on the NIAAA Web site. If all of the priorities are not funded in one year, the Institute may decide to continue them or to add additional funds: it is an ongoing and iterative process. It is not unusual for the priorities identified in the CJs to be continued in future years.

Dr. Caetano commented that face-to-face meetings of the Working Group members are important for discussing and coalescing their recommendations. Dr. Warren agreed that in-person meetings are desirable, but also thought closer linkages will all Council members needed to be established so everyone could contribute and potentially identify priorities deserving special consideration.

When Dr. Caetano asked whether there was some way to look at past priorities and decide about adding any new ones, Dr. Eckardt clarified that the priorities do have to be discussed each year as part of the congressional justifications. However, it would be simple to list all 30 or so possible areas of emphasis for several previous years and show Council members how these have been winnowed down and five high-priority ones selected for any additional funding. While these priorities are shared with Council through its Working Group, the final decisions are made internally and are posted on the Web as soon as they have been presented to Congress.

Dr. Warren reminded the audience that senior NIAAA staff members would be available to answer questions at an open session immediately following adjournment of the Council meeting.

Dr. Richard Suchinsky, Ex-Officio Representative from the Veteran’s Administration, reported the recent appointment of a new Under Secretary for Health, Dr. Robert Roswell. While it’s premature to predict his agenda for the VA’s healthcare system, the budgetary outlook is grim. More eligible veterans are requesting medical care than current funding can support. One initiative proposed to address this issue is the CARES project for capital asset restructuring which, in all likelihood, will close some VA medical centers and reallocate resources to locations where veterans are moving. Importantly, the CARES project will probably impact the VA research portfolio and infrastructure.

Dr. Roger Hartman, former Ex-Officio Representative from the Department of Defense—who just became a staff member of NIAAA—reported that DOD has ordered and delivered 197 copies of the American Society of Addiction Medicine (ASAM) Patient Placement Criteria to all military hospitals and clinics in its treatment system. The next step will be to train providers on using the rather intimidating document.

Ms. Sis Wenger, representing the National Association for Children of Alcoholics, distributed a package of materials this organization developed, with support from the Center for Substance Abuse Prevention (CSAP), for healthcare personnel in primary care settings. Pediatricians, family practitioners, and community health clinic staff are urged to ask every child who visits a single question, "Have you ever been concerned about someone in your family who is drinking alcohol or using drugs?" and then to respond appropriately with open-ended follow up questions or actions. The kit is designed to give office-based healthcare practitioners the necessary knowledge to implement a set of core competencies identified by medical leaders at a 1997 White House Conference for helping children in families affected by substance abuse. The materials include a special issue of Pediatrics explaining the competencies; seven tools that translate the competencies into specific activities and reference materials; background materials describing the nature and scope of the problem; and a reproducible handout brochure, It's Not Your Fault. NACA is undertaking a similar initiative with the faith community that will initially ascertain the competencies religious leaders need to intervene on behalf of children affected by a family member’s drinking or drug use.

Ms. Molly French, representing Partnership for Prevention, described the organization as encouraging public and private sector representatives to work together in developing and advancing policies and programs that protect and improve health. POP recently published an Issue Brief on Alcohol and Health that translates information on alcohol-related problems and associated interventions to reduce morbidity and mortality into specific actions that governments, businesses, and private sector leaders can take to prevent problems related to alcohol misuse. This Brief details some POP-identified gaps in research, including a better understanding of alcohol advertising effects on adolescents; cost effective ways to deter youth from initiating alcohol use; the best strategies to reduce alcohol dependency, binge drinking, and drunk driving; and a national system to track trends and patterns of alcohol use and related problems. To improve alcohol-related screening and counseling of patients in primary care settings—an intervention that prevention experts found to be as cost-effective as childhood immunizations and vision screening, but reaching less than half the target population—POP expects to work with the National Highway Traffic Safety Administration to encourage private sector employers and healthcare groups to include screening and counseling as part of routine care.

Ms. Thelma Thiehl, Chairperson of the Hepatitis Foundation International, described her concern about alcohol effects on the liver and the need to educate the public, particularly elementary school students, about the liver’s function and risk behaviors associated with cirrhosis and hepatitis. HFI, in conjunction with the Centers for Disease Control and Prevention has developed a series of seven videos on liver wellness, hepatitis, and substance abuse prevention. The first one targeting adolescents has been translated into Spanish, Vietnamese, and Mandarin, with special versions for African American youth, high-risk college students, patients at STD clinics, and offenders in detention centers and prisons. Additionally, HFI has developed a liver wellness program for corporations, made presentations to the College Health Association, and produced widely distributed public service announcements on preventing alcohol and substance abuse.

Mr. Gary Decker, Director of Programs for the Century Council, applauded NIAAA’s study of college drinking patterns and said the organization was proud to join the fight against underage drinking. As part of this effort, the Century Council will be publishing a revised version of Alcohol 101 in the fall. This interactive CD-ROM for college students that focuses on responsible decision-making with respect to alcohol is currently used on 1,200 college campuses nationwide, as well as in all the branches of U.S. military services and in 17 foreign countries.

The revision was developed with help from a panel of more than 30 national leaders, including on-campus practitioners, experts on public health and traffic safety, and representatives from NIAAA and the U.S. Department of Education. The new CD-ROM specifically targets college freshmen, Greek fraternity members on college campuses, student athletes, and offenders in the judicial system. An expanded Facilitators Guide and a supporting Web site will accompany the program.

Mr. Harlan Pruden, Project Coordinator for Speak Out: Lesbian, Gay, Bisexual, and Transgender Voices for Recovery, described this organization’s grassroots NYC efforts to enlist the recovering LGBT community in educating the public, treatment providers, and policy makers about applicable addiction and treatment issues. A major focus of Speak Out, which receives funding from CSAT and is a Recovery Community Support Program grantee, is the extensive stigma that impedes LGBT persons’ access to treatment and successful recovery. The stigma of sexual orientation and/or gender identity is often exacerbated by the added barriers of being female, a person of color, HIV-infected, disabled, or poor that contribute to the isolation that is a hallmark for addiction. The Department of Health publication, A Provider's Introduction to Substance Abuse and Treatment for LGBT Individuals, indicates that this group experiences a higher rate of addiction than the mainstream population and also that addiction among LGBT individuals may be linked to traumatic histories of childhood and adult abuse, rape, and violence. Because quantitative studies in this area are few and often flawed, Speak Out recommends more community-based research and empirical studies. Other needs for LGBT communities include safe drop-in centers that are alcohol- and drug-free; resources to update training curricula for providers, a comprehensive prevention plan that targets LGBT persons; and increased representation of LGBT persons in designing and implementing relevant programs.