Addressing Human Relevance in Research Related to Alcohol Use Disorders

Abstract

Alcohol use disorders (AUDs) remain a substantial public health problem. Although these disorders are best addressed through public health interventions, billions of dollars have been spent on research purported to examine the mechanisms and treatments of addiction in animal models. After this enormous investment, only three medications, limited in efficacy and carrying high risks, are available for individuals with AUDs. Despite decades of animal experimentation, the incidence of AUDs is on the rise. The National Institute on Alcohol Abuse and Alcoholism, the primary funder of alcohol-related research, should increase its focus on studies identifying methods to (1) prevent alcohol abuse, (2) develop behavioral interventions for those who are struggling with addiction, and (3) determine how best to implement these methods on a large scale. Focusing on human biology and behavior, rather than animal models, will more effectively address this uniquely human disease.

Relationship to Existing APHA Policy Statements

• APHA Policy Statement 2004-01: Reducing Underage Alcohol Consumption
• APHA Policy Statement 2004-09: Promoting Public Health and Education Goals through Coordinated School Health Programs
• APHA Policy Statement 201111: Prioritizing Noncommunicable Disease Prevention and Treatment in Global Health
• APHA Policy Statement 20129: Changing the Common Rule to Facilitate Multisite Research and Establish an Appeals Process
• APHA Policy Statement 201415: Support for Social Determinants of Behavioral Health and Pathways for Integrated and Better Public Health
• APHA Policy Statement 6210: The Utilization and Care of Animals in the Advances of Medical Science
• APHA Policy Statement 7222: Ethical Issues in Health Services Research and Development
• APHA Policy Statement 7513: Alcoholism
• APHA Policy Statement 8817(PP): A Public Health Response to the War on Drugs: Reducing Alcohol, Tobacco and Other Drug Problems among the Nation’s Youth

Problem Statement

Public health issues related to alcohol use disorders (AUDs): Alcohol abuse is a condition defined as “continued drinking despite negative consequences and the inability to fulfill responsibilities.”[1] In contrast, alcohol dependence is characterized by a craving for and possible physical dependence on alcohol, an inability to control one’s drinking, and an increasing tolerance to the effects of alcohol.[1] The latest edition of the Diagnostic and Statistical Manual of Mental Disorders integrates the two conditions into a single category labeled AUDs. AUDs are a substantial public health concern. Short-term risks include acute alcohol poisoning, increased violent behavior, drunk driving, and other risky activities. Chronic AUDs have been linked with liver, heart, and intestinal diseases; certain cancers; fetal abnormalities; neurological and psychiatric disorders; and social problems.[2] 

Binge drinking is an AUD defined as consumption of four or more alcoholic drinks on one or more occasions for women and five or more drinks on one or more occasions for men. This behavior is common among US adults and contributes to more than half of alcohol consumption.[3,4] Individuals who binge drink tend to do so frequently (an average of four times per month) and with high intensity (an average of eight drinks on one occasion), placing themselves and others at a significantly greater risk for alcohol-related harms.[4] Research shows that the incidence of binge drinking is on the rise.[5] 

Binge drinking prevalence and intensity are highest among people 18–34 years of age. While binge drinking is more prevalent overall in groups with higher incomes and higher educational levels, people with lower incomes and lower levels of educational attainment binge drink more frequently and heavily.[4] The prevalence of binge drinking is higher among non-Hispanic Whites (21.1% of the population) than among all other racial/ethnic groups (Black, non-Hispanic, 14.2%; Hispanic, 17.7%; Asian/Pacific Islander, 10.3%; American Indian/Alaska Native, 18.2%), but Native Americans report more binge drinking episodes per month (4.5 episodes) and higher alcohol consumption per episode (8.4 drinks) than other groups.[3,4] 

Members of marginalized communities, such as lesbian, gay, bisexual, and transgender (LGBT) people, are more likely to use alcohol and more likely to continue heavy drinking into later life. Reliable data on the LGBT community are difficult to obtain. With the limited data available, researchers estimate that approximately 20% to 25% of homosexual men and women are heavy alcohol users, as compared with 3% to 10% of heterosexual men and women.[6]

Efforts to address short-term risks have primarily focused on legal and social measures: limiting alcohol availability (e.g., reducing the number of outlets selling alcohol), implementing taxes, increasing the minimum drinking age, and strengthening blood alcohol content laws. Each of these measures has had a demonstrable, albeit limited, effect on alcohol abuse.[7–9] Between 2002 and 2011, the percentage of underage individuals reporting having consumed alcohol in the preceding 30 days dropped from 28.8% to 25.1%.[10] In this same period, the percentage of teens and adults who had driven under the influence of alcohol at least once in the preceding year decreased from 14.2% to 11.1%.[10]

Alcohol-related deaths have remained steady since 2002, at approximately 80,000 Americans per year.[11] The Centers for Disease Control and Prevention estimated that, in 2006, excessive drinking resulted in more than 1.2 million emergency room visits and more than 2.7 million physician office visits.[11] In 2011, alcohol consumption was estimated to lead to more than 2.5 million deaths each year.[2] 

Use of animals in AUD research: The broad scope of public health issues related to alcohol use has led to substantial investments in AUD-related research. One of the primary sources of funding for such research is the National Institute on Alcohol Abuse and Alcoholism (NIAAA). NIAAA administers approximately 1,400 grants at 250 institutions, accounting for about $490 million in annual grant funding. About 30% of NIAAA funding is devoted to clinical research programs related to prevention, treatment, and health services. According to the National Institutes of Health (NIH) RePORTER database (http://projectreporter.nih.gov/reporter.cfm), nearly 700 NIAAA grants, totaling more than $200 million per year, include animal experiments. 

While medications play a role in treating AUDs, only three medications to date have been approved by the Food and Drug Administration (FDA). Disulfiram induces aversion to alcohol,[12] but there may be severe side effects and potentially serious drug interactions. Its therapeutic benefit is inconsistent, so it is not widely used.[13] Naltrexone reduces the urge to drink by influencing the dopamine reward system.[12,14–16] Naltrexone use carries the risk of side effects such as hepatitis and liver failure.[12] Clinical trial data are inconsistent regarding naltrexone treatment outcomes, although some patients are less likely to engage in heavy drinking and have a longer time to relapse.[17] The most effective medication currently approved is acamprosate.[12] However, for optimal efficacy, acamprosate is prescribed to abstinent patients who have undergone detoxification.[18,19] 

There are a number of both ethical and scientific issues intrinsic to the use of animals in research. Laboratory and experimental conditions are inherently stressful. For example, rodents that have been handled by laboratory personnel exhibit increased heart rates, body temperatures, and circulating levels of stress-related hormones such as cortisol. Rats and mice exhibit stress-related behaviors such as excessive grooming and aggression and may develop stress-related gut inflammation.[20,21] Blood collection from rodents, rabbits, dogs, and nonhuman primates results in increased cortisol and blood glucose levels.[22–25] These changes in basal stress responses persist for hours or days after handling.[26] These animal stress responses and their physiological consequences likely affect experimental data and outcomes in unpredictable ways.

In particular, large animals used in research on fetal alcohol spectrum disorders (FASDs) are frequently subjected to multiple surgeries, long-term instrumentation, and frequent sample collections. Sample collection from nonhuman primates commonly results in overt fear responses, such as vocalizations and physical resistance.[26–28] A 2005 review of animal models of FASDs cited restraint stress in nonhuman primates as a confounding issue when interpreting data collected from these animals.[28] Importantly, simply witnessing the effects of these procedures may influence the basal stress responses of neighboring animals.[29–31] Overall, this research confirms that laboratory housing conditions and the procedures performed on animals cause significant fear and stress in the subjects and other animals nearby. The studies also alter the physiology of the animals, contributing to the unreliability of animal experiments for correlation with human biology. 

Specific to the ethics of FASD and other alcohol-related animal models is the issue of alcohol consumption. Animals used in alcohol-related experiments are sometimes induced to drink sweetened alcohol. They are also frequently injected or gavaged with extremely high doses of ethanol.[32–34] This can be considered unnatural from a human perspective and can induce unpredictable and unwanted stress responses in animals. In particular, oral gavage has been shown to cause changes in body temperature, hormone levels, and liver function in mice and rats.[35–37] Consumption of alcohol in rats has been linked to changes in the hypothalamic-pituitary-adrenal (HPA) axis, which plays a central role in stress responses.[32,38] HPA axis activation and increased corticosteroid production have been reported in nonhuman primates after ethanol administration as well.[39] Data reliability and translation to the human condition are unavoidably compromised by studying the effects of alcohol consumption in species that (1) would not spontaneously consume ethanol, (2) metabolize ethanol differently, (3) receive ethanol via different routes than humans, (4) have different genetic and physiological characteristics, and (5) exhibit stress responses caused by inappropriate housing conditions, frequent handling, and alcohol consumption itself.[40] Above and beyond the ethical implications, the vast majority of animal models of AUDs are remarkably far removed from alcohol abuse as it occurs in humans.

Regarding animal models of FASDs, genetic and physiological differences hinder the translation of results from the animal laboratory to the clinic. FASD research is conducted in species ranging from worms to nonhuman primates. Several species, such as worms, flies, and zebrafish, are utilized for their relative simplicity and rapid reproductive cycle. However, all of these models lack a placenta, a significant deviation from human biology.[28,41] 

While placental mammals such as rodents, sheep, and nonhuman primates are often used in FASD research, many genetic and physiological differences remain of concern. The rates of brain growth in rats, mice, sheep, and nonhuman primates differ significantly from the rates among humans. For example, a rhesus macaque is born with 76% of its adult brain weight, while humans are born with only 27% of adult brain weight.[42] 

NIAAA funds FASD research at approximately $30 million per year. More than half of this funding is allocated to research studies involving animal models. A search of the literature indicates that, between 1970 and 2014, more than 4,000 FASD studies were published. However, only 72 were clinical studies, and only two of those investigations tested a pharmacological agent as opposed to a new screening or therapy strategy.[41]

In the past decade, the number of compounds in drug development in all fields has increased by 62% and total research and development spending has doubled, but the average number of FDA-approved new drugs per year has declined.[43] Recent studies indicate that the average drug-development failure rate is 56% for phase I, 82% for phase II, and 50% for phase III, a cumulative failure rate of 96%.[44–47] Developing a new prescription medicine, a process that often requires longer than a decade, is estimated to cost $2.6 billion,[48] with taxpayers indirectly paying for about 39% of company research and development through federal funding.[49] Even if the true expense of bringing a new drug to market may be much lower, with evidence suggesting that the actual cost might be several hundred million dollars,[49] this is an unsustainable cost that reflects, among other factors, the high attrition of drug candidates. This is in part due to misleading results from animal testing that have led to human drug trials with little chance of succeeding. In addition, even if a new AUD drug is approved for market, no drug is effective for all patients. The addiction medications on the market are at best useful 30% to 35% of the time.[50] Because of the complexity of AUDs and the overall poor correlation between preclinical research and clinical practice, the treatment efficacy of an approved medicine can vary significantly among individuals.[51] Even if a new AUD medication is available in the future, it is unlikely to be cost-effective considering the high cost and high failure rate of drug development and the low pharmacotherapeutic efficacy. 

Ethical considerations related to the involvement of human participants in AUD research: When AUDs are studied through human-based approaches (i.e., studies involving human research participants, human epidemiological data, or human cells and tissues), the regulations for protection of human participants—the Common Rule (45 CFR 46)—or the FDA’s similar regulations should be followed if applicable. As explained in the Belmont Report, the ethical principles that underlie these regulations, including respect for persons, beneficence, and justice, can help guide the design and conduct of the research as well as the application of the regulations. Beyond this, however, Emanuel and colleagues have recently consolidated the ethical research guidance offered in a number of codes, declarations, and regulations over the past 70 years. Specifically, they have distilled and refined these ethical guidelines into an eight-principle framework: (1) collaborative partnership, (2) social value, (3) scientific validity, (4) fair participant selection, (5) favorable risk-benefit ratio, (6) independent review, (7) informed consent, and (8) respect for participants.[52] Both the principal investigator and the institutional review board are responsible for the development and implementation of ethical research protocols.   

In addition to general ethical principles and standard protections for research participants, there are ethical concerns that apply specifically to AUD research. For example, in general alcohol should not be administered to alcohol-naïve participants owing to the unknown level of risk. Risks and benefits should be carefully evaluated before alcohol is administered to individuals who may be more vulnerable and have a higher risk of developing AUDs (e.g., individuals with at-risk familial and/or genetic backgrounds or a family history of AUDs). Careful evaluation is needed in the case of participants who already have an AUD. In particular, investigators need to address the following essential issues: “medical examination and screening to assure the absence of any medical or mental condition for which further alcohol exposure at the dose contemplated would be contraindicated [and] assessment of current treatment-seeking status, duration of abstinence within the treatment regimen and the risks entailed through exposure to alcohol.”[53] 

Moreover, involvement of women of childbearing potential and young adults should be cautiously evaluated. Before each alcohol administration, the possibility of pregnancy should always be assessed via a urine hormonal assay. Women who are pregnant must be excluded from participation.[53] There is no documented safe amount of alcohol to consume during pregnancy, and there is no time during pregnancy when it is safe to drink.[54] Epidemiological studies show that, in the United States, AUD prevalence is at its highest during late adolescence.[4] Therefore, there is a need to study this population. However, a number of studies have shown that adolescent brains may be particularly vulnerable to alcohol-related harms.[55,56] If late adolescents are included as research participants in alcohol administration studies, the potential benefits for them and for society must outweigh the risks. For instance, investigators should offer clear justifications on how their study can inform prevention and treatment by providing a better understanding of the effects of alcohol on young adult drinkers. Precautions such as decreasing the number of doses of alcohol administered must be taken to minimize the risk to participants.[53]

It is crucial to recognize and manage the ethical issues associated with research involving human participants. Through decades of effort, a comprehensive guideline and evaluation system has been established. Nevertheless, there is room for improvement and a need for large-scale clinical and intervention studies. Consequently, current US alcohol research strategies should be refocused taking into account human-based studies, which have generated successful and cost-effective prevention and intervention outcomes. Decades of research on animals have failed to produce significant benefits for human patients struggling with addiction. The medications that have been developed have limited efficacy and substantial adverse effects. While prevention and intervention studies in a variety of human populations have proven successful, a dearth of funding for implementation research has resulted in a failure to capitalize on these developments. Successfully ameliorating the AUD public health crisis is possible only by redirecting attention more fully to humans, studying how to prevent and treat alcohol abuse disorders, and discerning how best to implement these measures at the population level. 

Evidence-Based Strategies to Address the Problem 

Prevention and intervention studies among humans to address human relevance in AUD research: A number of prevention and intervention studies have been published within the past several years that outline effective methods for reducing the impact of harmful drinking. Systematic reviews indicate that behavioral counseling interventions improve behavioral outcomes among individuals with AUDs.[57–59] Behavioral therapies include goal setting, self-monitoring of drinking, analysis of drinking situations, and acquisition of alternative coping skills. Couples and family therapies focus on drinking behaviors and aim to improve relationship factors, such as improving communication, avoiding conflicts, and learning to solve problems that might lead to drinking. Core components of effective therapies include building social support, working with patients to develop goals and providing them with ideas for reaching those goals, modeling and rewarding good behavior, and reviewing ways to cope with triggers that lead to drinking.[60] 

Despite the promise shown by these programs, they are not being implemented on a large scale. Several examples follow. 

As FASD is very likely a preventable condition, many studies have focused on educating women of childbearing age to avoid alcohol consumption or to use contraception. A 2011 study tested the efficacy of a Web-based assessment and intervention tool among women of childbearing age receiving WIC (Special Supplemental Nutrition Program for Women, Infants, and Children) benefits. Participants received either personalized feedback or general information regarding alcohol use and pregnancy. Interestingly, both groups showed a significant decrease in risky drinking behavior.[61] A similar study examined the effects of telephone versus in-person brief interventions on alcohol and contraceptive use among women of childbearing age.[62] Again, both groups showed a decrease in risky drinking behavior and an increase in contraceptive use, indicating that relatively simple interventions, if implemented on a larger scale, may reduce FASD prevalence. 

An international study conducted in New England and the Czech Republic assessed the effectiveness of computerized screening and brief advice from a health care provider in reducing alcohol consumption among youths 12 to 18 years of age.[63] Participants completed the computerized screening and were then provided screening results, scientific information, and real-life stories illustrating the harms of substance use. Health care providers also received screening results, as well as specific talking points to prompt brief advice to the participant. Relative to treatment as usual, New England participants reported less alcohol use, and Prague participants reported less cannabis use.[63] This study highlights both the promise of new interventions to reduce adolescent substance use and the need for population-specific research.

One particular population for which specialized treatment is required is individuals with both AUDs and mental illness. A pilot study of Creating Change, a treatment program designed for individuals with both substance use issues and posttraumatic stress disorder (PTSD), has proved promising. This behavioral therapy model resulted in improvements in PTSD-related symptoms, such as anxiety, depression, and psychopathology, as well as alcohol and other substance use. Creating Change is based on the successful Seeking Safety group behavioral therapy model, also created for individuals with PTSD and substance use issues. Studies among both male civilians and male veterans have shown promise in reducing PTSD-related symptoms as well as alcohol use.[64–66] 

Need for large-scale implementation studies: Large-scale implementation studies focused on AUD prevention and intervention will foster evidence-based public health policy and program development on a lasting basis. An example of a large-scale implementation study is the Swedish Risk Drinking Project, a national study with broad coverage of Swedish health care providers. This investigation targeted employees within primary health care (i.e., general practitioners, residents in family medicine, district nurses), child health care (i.e., nurses), maternity health care (i.e., midwives), and occupational health care (i.e., occupational physicians and occupational nurses) services.[67] The size and scope of such studies will depend on multiple factors, such as the setting of the study (e.g., home, school, workplace) and population demography.  

Health economic evaluations have shown that nonpharmacological treatments, such as brief motivational counseling that includes motivational enhancement therapy, are cost-effective[68–71] and can save approximately five times as much in spending on health, social, and criminal justice services as they cost.[68] There is substantial evidence on the effectiveness of different policies in reducing alcohol-related harm. Population-based legal and social interventions (such as tax enforcement or random breath testing) have been shown to be highly cost-effective alcohol policies and are recommended by the World Health Organization.[71]

Mutual-help groups and behavioral treatments are often effective. However, continued research is needed to improve treatments, determine which approaches are most successful with which subpopulations, and learn how to make effective therapy available to patients of all income levels and demographic groups. Clinical trials examining the efficacy of mutual health groups or behavioral therapies alone or in combination with medications will help guide clinical practice.

Research involving human participants needs to take special precautions to ensure, as much as possible, that benefits outweigh risks. Investigators are forbidden to select participants merely because of ease of availability, low social or economic status, or limited capacity to understand the nature of the research. Crucial precautions include the need to consider the participant’s age, gender, familial or genetic background, prior alcohol use, other drug use, and general medical and psychological condition.[53] The NIAAA guideline on administering alcohol in human studies (see http://www.niaaa.nih.gov/research/guidelines-and-resources/clinical-trial-regulations-policies-and-guidance) outlines procedures to protect human participants in AUD research. 

Regarding the implementation of legal and social interventions, many US states have enacted policies aimed at reducing binge drinking. These measures include increasing taxes; implementing stricter drunk driving laws; restricting the days or hours of alcohol sales at restaurants, bars, and retail stores; limiting the number of outlets that sell alcoholic beverages in a given geographic area; and holding retailers responsible for problems caused by selling alcohol to visibly drunk customers or underage individuals. A recent study showed that states with stronger policies had less binge drinking.[72]

Opposing Arguments

There are four primary arguments one might expect in response to the recommendation that AUD research focus on human biology and behavior rather than animal models:

1. Medications to treat addiction cannot be developed without animal models.
2. Prevention of AUDs is important, but medications are still required for treatment. 
3. NIAAA already funds prevention and intervention research.
4. The use of animals has taught us much about the neurological mechanisms of addiction and abuse.

The following counterarguments are provided to refute these points.

The numerous physiological differences between humans and other species render it unlikely that new, successful drugs for the treatment of addiction will be discovered through animal models. It is a common assumption that animal models are required for the development of new medications. However, of the three medications currently approved by the FDA for the treatment of alcohol addiction, only two were developed in laboratory animals.[73] Scientists using animal models for the development of medications do so under the assumption that modeling specific characteristics of alcohol addiction and other diseases will enable the identification of effective compounds.[74] However, fewer than 10% of all drugs entering clinical trials will ultimately be approved by the FDA, and neurological drugs entering phase I trials also have less than a 10% likelihood of approval.[75] Over the past 20 years, more than 100 different drugs have shown promising results in animal models of alcohol addiction, leading to nearly 150 NIH-sponsored clinical trials but only a few, suboptimal drugs. 

Regulatory agencies, recognizing the limitations of animal tests, have made strides to become more flexible and discerning regarding the information they request. The FDA investigational new drug guidance indicates that applicants “can use an alternative approach if that approach satisfies the requirements of the applicable statutes and regulations.”[76] The FDA also encourages scientists to conduct predevelopment meetings to determine information needs and avoid animal tests. It is always in the purview of applicants to offer nonanimal testing that may be accepted by regulatory agencies.

In the absence of an effective way to develop compounds that are effective in humans, resources are best allocated toward preventing and treating AUDs through behavioral interventions. The high cost of drug development and the high failure rate of clinical trials make it difficult to foresee cost-effective pharmacotherapy being developed under current drug-development procedures. The development of AUDs is a complex process that involves multiple genes and epigenetic effects and various environmental interactions.[77] The treatment efficacy of pharmacotherapies varies among individuals, with a 30% to 35% success rate for treatment of addiction, including AUDs.[50,51] Moreover, AUDs are systemic behavioral disorders developed from psychological, social, and biological processes that cannot be replicated in animal studies. Individuals with AUDs need to deal with the stressful experiences of everyday life and to experience positive and pleasurable moments in social interactions without the use of alcohol. Hence, to prevent and treat AUDs, current research efforts should focus on the development and testing of psychosocial strategies that can be used to learn coping skills.[78] Reliance on medications does not appear to be the most reliable and cost-effective strategy to cure or control AUDs.

While the NIAAA does fund prevention and intervention studies, fewer than half of all clinical studies funded in fiscal year 2014 fell into this category. The majority were drug trials, and few NIAAA-funded studies sought to implement successful techniques in different populations or on a larger scale. The absence of funding for implementation studies is a failure to capitalize on the initial investment in smaller clinical studies. 

For instance, as noted above, NIAAA funds approximately $30 million in FASD research per year. In 2014 alone, approximately 68% of this funding was allocated for research involving FASD animal models, as indicated in the NIH’s RePORTER database. A systematic review of interventions for children with FASD indicated that among the 6,263 FASD studies identified in a literature search, researchers could include only 12 intervention studies in their analysis. Although virtual reality training, cognitive control therapy, language and literacy therapy, mathematics intervention, and rehearsal training for memory may be effective, there is limited high-quality evidence of specific FASD interventions.[79] More human-based research is needed to maximize the positive impact of evidence-based behavioral interventions in order to benefit society as a whole, as well as to foster evidence-based health policy and program development on a lasting basis. The NIAAA and other funding bodies should reprioritize their grant portfolios to fund these essential studies rather than continuing to funnel funding into animal-related studies with poor translational capacity. 

Finally, while the study of animal models of alcohol addiction has led to the publication of thousands of scientific papers, it is difficult to say how much these studies have contributed to our understanding of human addiction. Neurobiological models, based mostly on data from rodent studies, cannot mimic specific aspects of the human condition and can reflect underlying biological processes different from the clinical pattern. Interspecies differences can lead to potential treatments that target inappropriate aspects of alcohol-related behaviors.[34] Few medications are available to treat the addiction itself, and those that are available have limited efficacy and serious side effects.[50,51,80] Although neurological aspects are crucial, they are not sufficient to explain, prevent, or ameliorate human-related AUD behaviors.[78] More reliable and cost-effective interventions for individuals with AUDs are behavioral and psychosocial.[57–59] These methods have been developed by studying humans with actual AUD issues rather than animals that have been trained or forced to consume large quantities of alcohol. 

Action Steps

Given that the mission of APHA is to “improve the health of the public and achieve equity in health status,” it is recommended that:

1. The NIAAA declare that addressing human relevance, through the implementation of human-based strategies, is a priority in AUD research and reflect this priority in its research funding. In this context, “return on investment” analyses are needed to judge the efficacy and reliability of traditional research models—especially animal models—and to identify and undertake new research avenues. In particular, large-scale clinical studies focused on prevention and education might represent effective approaches to fostering knowledge of the biological, psychological, and sociological components of alcohol addiction and AUDs. 
2. The NIAAA allocate more research funding toward human-based, as opposed to animal-based, studies. The focus should be on intervention strategies aimed at treating and preventing AUDs, especially in at-risk populations such as women, adolescents, and individuals with low incomes. This reallocation should include greater scrutiny of studies that have not translated or are unlikely to translate to improvements in prevention, intervention, or public education programs. 
3. The NIAAA launch a public education program to increase the overall level of awareness about the risks related to alcohol consumption and addiction, with a close focus on more vulnerable populations.
4. Congress mandate that prevention of alcohol abuse be a national research priority by endorsing AUD research that accounts for human relevance and the pivotal role of prevention. Return on investment analyses should be considered in order to judge the efficacy and reliability of research models, especially animal models.

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