Sylvia Baedorf Kassis, MPH
Project Manager, Neurological Clinical Research Institute, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
Instructor, Master of Science in Clinical Investigation (MSCI) Program, Boston University School of Medicine, Division of Graduate Medical Sciences, Boston, MA, USA
Alcohol use disorders are associated with significant health and social consequences; their study has become a national research priority, but not without controversy. The National Institute on Alcohol Abuse and Alcoholism supports research involving the administration of alcohol to human subjects as a critical experimental approach to addressing the etiology, treatment, and prevention of alcohol use disorders.1 Studies examining the effects of alcohol have the potential to increase understanding of the factors that influence alcohol consumption and unhealthy use, as well as potentially mitigate these effects.2 Some studies, however, may raise ethical concerns, especially when considering the strength of the hypothesis being tested, study design, cohort selected, study risk profile, and validity of the informed consent process. While there is a wide range of research involving the administration of alcohol that could be discussed in relation to the aforementioned topics—including studies of healthy college students3 and the administration of ethanol to prevent alcohol withdrawal syndrome4—the primary focus of this article will be on addressing the ethical issues surrounding one of the more controversial types of alcohol administration studies: enrolling people who engage in heavy drinking and/or those with an alcohol use disorder.
Since the first systematic review of the physiologic effects of alcohol was published in the 1950s, there has been a long tradition of scientific research based on the administration of alcohol to human subjects that has advanced understanding of alcohol’s effects in areas such as aggression, information processing, and perceptions of risk-taking.5,6 Further, several treatment approaches have been investigated via the administration of alcohol to alcoholics.6 Despite this rich history of research experience in the field, and in light of past research abuses, it is not uncommon to find ethics boards taking a more protectionist stance when reviewing alcohol administration studies. Thus, it is helpful when considering such research to anticipate the major ethical questions that may be raised and to be prepared with thoughtful, well-reasoned responses that address the potential concerns.
The importance of the hypothesis being tested
When developing the study idea, a careful review of the literature and a well-articulated rationale for how the proposed study will further understanding of the issue and expand the knowledge base are crucial. The more controversial the subject area, the more important it is for researchers to be able to describe the data that exists, the ways in which they are insufficient, and how the research study posits to fill a gap in the literature. While not at all unique in the research approval process, in the case of alcohol administration studies enrolling people with unhealthy alcohol use, this kind of justification is essential to alleviating the concerns of ethics boards that might question the societal value of the research question under investigation.
The appropriateness of the study design
The process by which the study question will be answered warrants a complete explanation so that the methodology being used to assess the hypothesis is robust and scientifically valid.6 The involvement of biostatisticians and other design experts who are familiar with alcohol administration studies is essential to ensuring the soundest methodological approaches are selected and any limitations to the proposed procedures addressed completely.
The enrollment of only the most suitable subject population
Closely related to the validity of the hypothesis and study design is the need for a full justification of the subject population to be recruited into the study. While in research ethics there is always a consideration of the Belmont Principle of Justice in the enrollment of study participants, studies that have the potential to include individuals considered particularly vulnerable and in need of protection frequently undergo a more careful review. To this end, it behooves investigators to develop study inclusion and exclusion criteria that carefully weigh out the potential consequences of research participation. In general, for alcohol administration studies among those with unhealthy alcohol use, the participants should be those not in, or seeking treatment or working on quitting drinking as exposure in those people could thwart their efforts. These participants are likely to continue drinking, no more or no less, after alcohol is administered as part of a study protocol.
A complete assessment of potential risks and benefits
To justify alcohol administration studies in people who may have an alcohol use disorder, the risks to individual participants must be weighed against the potential benefits to themselves and society. While the assumption has been that the administration of alcohol in a study population is detrimental to wellbeing and sobriety, almost all of the studies that have evaluated research participants following exposure to alcohol have failed to identify adverse effects on subsequent drinking behavior and psychosocial adjustment.6 So, the question becomes: Can we place individuals at possible risk in order to answer a question that may not benefit them directly, but could impact our understanding of alcohol dependence and/or therapeutic options moving forward?
It should also be noted that some research participants have reported personal benefit from their participation in these studies, including heightened self-esteem, acknowledgement of denial, and access to free treatment. While these are certainly valid feelings, the fact that most research is designed not to benefit the individual, but to answer a specific research question and contribute to generalizable knowledge, must be reiterated to the participant during the consent process and over the course of the study. That noted, studies involving alcohol administration to people with heavy drinking or alcohol use disorders should all offer participants help with their drinking at the conclusion of the study.
A well-conducted, well–documented, and informed consent process
Tucker and Vuchinich (2000) describe obtaining informed consent from people with unhealthy alcohol use within the disease model that generally asserts (erroneously, according to the authors) alcohol use disorders are prima facie evidence that an individual’s decision-making capacity is impaired. In contrast to the aforementioned view, these authors report that a proper research context that emphasizes environmental influences on behavior, as opposed to stable biological or personality dispositions, allows for non-coercive informed consent.7 They go on to argue that these views, while well understood in certain segments of the alcohol research community, are not necessarily accepted by other scientists, professionals, and lay persons who may sit on ethics boards.
Thus, when considering alcohol consumption studies enrolling people with heavy drinking and/or alcohol use disorders, ethics boards will likely ask to review a detailed description of the consent process. Further, because some may question the ability of this population to give fully informed consent, they will expect the principal investigator to be able to address how the research team will ensure valid consent is obtained and coercion is avoided.
There is no question that research studies involving the administration of alcohol to human subjects have their place in the study of alcohol use disorders. It is essential, however, before undertaking such a research endeavor, to consider the results of relevant past studies and ensure ethical principles have been adhered to in the study design, selection of participants, assessment of risks and benefits, and in the informed consent process.
1. National Institute on Alcohol Abuse and Alcoholism. Administering Alcohol in Human Studies. Available at: http://niaaa.nih.gov/Resources/ResearchResources/job22.htm.
2. Penslar RL (ed). Research Involving Human Subjects: The Administration of Alcohol. Research Ethics: Cases and Materials. Bloomington and Indianapolis: Indiana University Press, 1995. 105–111.
3. Howland J, Rohsenow DJ, Greece JA, et al. The effects of binge drinking on college students’ next-day academic test-taking performance and mood state. Addiction. 2010;105(4):655–665.
4. Dissanaike S, Halldorsson A, Frezza EE, et al. An ethanol protocol to prevent alcohol withdrawal syndrome. J Am Coll Surg. 2006;203(2):186–191.
5. Wood MD and Sher KJ. Risks of alcohol consumption in laboratory studies involving human research participants. Psychol Addict Behav. 2000;14(4):328–334.
6. Dolinsky ZS and Babor TF. Ethical, scientific and clinical issues in ethanol administration research involving alcoholics as human subjects. Addiction. 1997;92(9):1087–1097.
7. Tucker JA and Vuchinich RE. Creating a research context for reducing risk and obtaining informed consent in human alcohol studies. Psychol Addict Behav. 2000;14(4):319–327.