Sylvia Baedorf Kassis, MPH,* and Mary-Tara Roth, RN, MSN, MPH**
*Regulatory Education Manager and **Director, Clinical Research Resources Office, Clinical and Translational Science Institute, Boston University School of Medicine/Boston Medical Center, Boston, MA, USA
Obtaining informed consent to conduct research on people with alcohol and other drug (AOD) dependence can be challenging. Factors to consider include study type and design, anticipated risks and benefits of participation, and the subject’s capacity to consent. Although vulnerability of the study population must be considered in any research study, it is especially important in addiction research. Individuals with addictions are often socially marginalized and must be protected from any further stigmatization and social harm that might result from participating.1 Potential subjects may also have comorbid psychiatric disorders, may be socioeconomically disadvantaged, and may be susceptible to therapeutic misconception (i.e., they may assume the intent of the study is to provide treatment).1,2
Although an addiction diagnosis does not automatically preclude obtaining informed consent, researchers should be aware of the complexities inherent in working with vulnerable populations where there is legitimate concern as to whether subjects do, in fact, have the capacity to consent. The intent of this article is to provide information and guidance on respect for autonomy, consent capacity, and the informed consent process in AOD addiction research.
Types of Addiction Research Studies
A variety of study designs are used in addiction research, including interviews and surveys, tissue-banking epigenetic studies, neuroimaging, and testing of care-delivery models and medications—even administration of the drug of addiction, as in the Swiss Heroin Study.3,4 Although the latter help researchers understand the physiologic effects of addictive AOD, such studies present the most difficult ethical dilemmas.5 They also often enroll nontreatment-seeking persons, while the former tend to enroll those seeking treatment. This article focuses on addiction research that does not include emergency care patients, who are likely to have compromised capacity to consent because of intoxication or withdrawal. Proxy consent may be required in such patients, involving complex ethical issues beyond the scope of this article. Similarly, consent for research assessing the effects of drugs of abuse, as in the Swiss Heroin Study, is reserved for a separate discussion.
Ethical Principles in Addiction Research
The Belmont Report,6 which provides the foundation for current US human-subjects research regulations, defines the principle of “respect for persons” under which autonomy is captured. Autonomy means the actions of rational individuals must be respected, not interfered with, and decided upon without coercion or force.7 In respecting autonomy, the following ethical principles must be considered:
- free and voluntary participation,
- protected privacy and confidentiality, and
- comprehensible presentation of the potential risks of participation.
These principles are not only important in their own right; there are compelling scientific arguments as to why they must be respected as well. Studies that fail to adequately address vulnerability, fail to stress that participation is voluntary, or fail to ensure privacy and confidentiality protections have been enacted are less likely to produce reliable data.7 These tenets are especially salient in addiction research. For example, to protect privacy and confidentiality, investigators should collect only the minimum necessary information from participants, code and store data securely and separately from a master-code key linked to identifiers, and guard against subpoena with a Certificate of Confidentiality.
Components of Valid Informed Consent
As outlined in the Nuremberg Code, potential research subjects “should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision” 8 prior to enrolling. Yet, despite having undergone the informed-consent process, subjects frequently cannot report the risks or purpose of a study.9 Comprehension may be limited by comorbid conditions or by complex research designs that are difficult for individuals with limited experience in medical environments to understand. Thus, for valid informed consent to occur, the researcher must ensure that, in addition to imparting information, subjects have an adequate understanding of what that information means for them; i.e., consent must be competent, voluntary, informed, and comprehensible.10
Components of Consent Capacity
Decision-making capacity is the ability to understand and appreciate the consequences of health-related decisions and to formulate and communicate those decisions.11 When faced with a decision that is particularly complex (e.g., participation in research that involves a complicated study design or that carries potentially significant risks), a person may not be capable of making the decision.12 With regard to research participation, capacity to consent consists of the following components13–15:
- Understanding: having the facts needed to make a decision.
- Appreciation: being able to associate those facts with the potential effects on the individual.
- Reasoning: being able to weigh risks and benefits.
- Choice: being able to make one’s decision known.
Effects of Addiction on Consent Capacity
Appelbaum16 made the case that a diagnosis that affects cognition (for example, Alzheimer Disease) is not necessarily predictive of incapacity to make medical decisions. Likewise, while use of AOD may impair cognitive ability, there is a range of severity associated with drug use and addiction, such that use of a drug, or the condition of being addicted to a drug, is not in and of itself predictive of incapacity. Further, assessment of capacity depends on the state of the individual at the time consent is signed; as Saks and Jeste13 noted, the consent process is a “state,” not a “trait.” Capacity to consent may fluctuate over time.
Addiction researchers should recognize that potential subjects may be signing the consent form under the influence of substances of abuse; thus, cognition (and by extension, consent capacity) may be impaired. Tolerance to a substance may minimize a drug’s effect on cognition, which is why testing for the presence or level of a substance cannot be the sole determinant of whether an individual has capacity or not. Alternatively, the judgment of potential subjects who have not taken a drug within their usual timeframe could be impaired by withdrawal.
Recommendations for Informed Consent
The Nuremberg Code also states that “the duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs, or engages in the experiment.” 8 The researcher is responsible for assessing the decision-making capacity of potential subjects. A consent process that is properly supported can enable even those with diminished capacity to come to an autonomous decision regarding participation.12
The following is a compilation of best-practice recommendations to ensure a well-supported informed consent process.1,17–20
- Provide subjects with all the information they need to make a voluntary and informed decision.
- Use language that is understandable.
- Use audiovisual tools or simple summaries to increase comprehension and ease stress.
- Foster a noncoercive environment.
- Avoid therapeutic misconception by underscoring treatment versus research procedures.
- Provide multiple learning trials about particular aspects of the study (purpose, risks, benefits, alternatives, etc.); then provide corrected feedback.
- Use the teach-back method (i.e., the subject explains the study to the researcher).
- Implement an ongoing consent process throughout the study.
- Consider individual mental and physical conditions and motives and how they might affect consent capacity.
- In populations where diminished capacity may be prevalent, a simple query asking what the study is about or administration of the Mini-Mental State Exam could be used to determine the need for a more formal assessment of capacity. A brief 3-item questionnaire asking about study purpose, risks, and benefits could also be used.
- If questions remain about a potential subject’s ability to give informed consent, a qualified independent clinician, ethical consultant, or uninvolved third party should be asked to make an independent evaluation.
- When a more formal test of capacity is needed, consider using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR),20 a semistructured interview-based instrument.
Although including AOD-addicted individuals in research studies poses ethical challenges, it does not make the conduct of good, ethical research impossible. Attention to factors that support the consent process increases the likelihood that individuals with substance use disorders are able to provide meaningful valid consent. Tools are available to help investigators accurately assess a given individual’s capacity to do so.
1. Carter A, Hall W. Addiction Neuroethics: The Promises and Perils of Neuroscience Research on Addiction. Cambridge, UK: Cambridge University Press, 2012.
2. Appelbaum PS, Roth LH, Lidz CW, et al. False hopes and best data: consent to research and the therapeutic misconception. Hastings Cent Rep. 1987;17(2):20–24.
3. Perneger TV, Giner F, del Rio M, et al. Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments. BMJ. 1998;317(7150):13–18.
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6. National Institutes of Health Office of Human Subjects Research. The Belmont Report-Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Bethesda, MD: OHSR, 1979. Available at http://ohsr.od.nih.gov/guidelines/belmont.html.
7. United Nations Office on Drugs and Crime. Ethical challenges in drug epidemiology: issues, principles and guidelines, 2004. Available at: http://www.unodc.org/pdf/gap_toolkit_module7.pdf.
8. Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol. 2:181–182. Washington, DC: US Government Printing Office, 1949. Available at www.hhs.gov/ohrp/archive/nurcode.html.
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11. Veterans Health Administration National Center for Ethics in Health Care. Ten Myths about Decision-Making Capacity, 2002. Available at www.ethics.va.gov/docs/necrpts/nec_report_20020201_ten_myths_about_dmc.pdf
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14. Buchanan A. Mental capacity, legal competence, and consent to treatment. J R Soc Med. 2004;97(9):415–420.
15. Stanford Encyclopedia of Philosophy, Decision-Making Capacity, 2011. Available at: http://plato.stanford.edu/entries/decision-capacity.
16. Applelbaum PS. Assessment of patients’ competence to consent to treatment. N Engl J Med. 2007;357(18):1834–1840.
17. National Advisory Council on Drug Abuse. Guidelines on Administration of Drugs with Abuse Potential to Human Subjects, 2000. Available at: http://m.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.
18. Carter A, Hall W. The issue of consent in research that administers drugs of addiction to addicted persons. Account Res. 2008;15(4):209–225.
19. Palmer BW, Dunn LB, Appelbaum PS, et al. Assessment of capacity to consent to research among older persons with schizophrenia, Alzheimer disease, or diabetes mellitus: comparison of a 3-item questionnaire with a comprehensive standardized capacity instrument. Arch Gen Psychiatry. 2005;62(7):726–733.
20. University of California San Diego (UCSD) Task Force on Decisional Capacity. Decision-making capacity guidelines. Available at: http://irb.ucsd.edu/decisional.shtml.