Ensuring Subject Competence to Enroll and Participate in Addiction Research
Brenda Heaton, PhD, MPH
Assistant Professor, Department of Health Policy & Health Services Research, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA, USA
The necessity of obtaining research subjects’ voluntary and informed consent is a cornerstone of ethical clinical research that includes people with alcohol and other drug (AOD) dependence.1,2 The issue is particularly salient for these populations since participants’ capacity to provide consent may be in constant flux as a function of current intoxication, acute withdrawal, and comorbid psychiatric conditions, among other factors. For these and other reasons, equipping individuals with the necessary information to consent to research and make an informed decision can be complicated. Previous feature articles in this newsletter have recognized the many complexities of obtaining consent in AOD research3 as well as the unique issues related to consenting to administration of the drug of addiction.4 This article highlights the challenges and importance of ensuring the capacity to consent to AOD research by providing an overview of issues specific to this population and ethical expectations. We also discuss briefly tools and approaches that investigators can use to ensure appropriate informed consent.
Consent Capacity and AOD Research
Valid consent to participate in research hinges on “decisional capacity,” an adult’s ability to understand the necessary information, appreciate the impact of the information, weigh (reason) the risks and benefits and, ultimately, to make a voluntary choice about treatment or participation in research.5,6 For the purposes of this article, we will use the term “consent capacity” to refer to the above. In order for consent capacity to be attained, an individual must possess all four of these often-cited components at the time of consent. The extent to which the subject possesses them is a function of unpredictable physical and nonphysical circumstances since consent capacity is not a trait that can be assigned to an individual, but rather a state of being.5 More specifically, just because someone meets criteria for AOD dependence or has recently used a substance does not mean they do not have the capacity to consent.
Consent capacity is usually a function of how complex the research protocol is and the mental and/or physical state of the potential subject. For example, a person will have a greater consent capacity for research that is straightforward, of minimal risk, and is presented in a clear manner, compared with research that is high risk with a complex design and greater subject involvement. Conditions such as current intoxication, dementia, emotional duress, or withdrawal can modify a person’s consent capacity at any given time. Interestingly, a commonly held belief among AOD researchers is that people with drug dependence are able to give voluntary and informed consent if they are not under the influence of drugs or acutely suffering from withdrawal symptoms at the time of consent. It is also common for some to assume that any evidence of recent use (e.g., breath alcohol) means that a participant does not have the capacity to consent. However, there is significant variability in individual responses to drugs and drug withdrawal. One’s capacity to consent, therefore, must take into account at least two contributing factors: The complexity of the research design, and the cognitive, physiologic, and motivational states of the individual. Consequently, investigators should expect a great amount of variability in consent capacity among populations with AOD dependence and therefore it should be assessed and not assumed.
Ethical Framework: Justice, Beneficence, and Respect for Persons
The Belmont Report7 is the guiding document for human subject research regulations in the United States. It provides three fundamental principles for the ethical conduct of human subjects research: Justice, Beneficence, and Respect for Persons. Although voluntary and informed consent is often cited as the hallmark of Respect for Persons, the issue of consent capacity traverses all three of the principles, which should be kept in mind in order to protect the rights of participants.
Justice: The burdens and benefits of research should be fairly distributed
It can be tempting for AOD researchers to simply restrict their research populations to those individuals who are most likely to be capable of consent. For example, they may exclude potential subjects with co-morbid psychiatric conditions known to be associated with diminished consent capacity. However, as Geppert notes, “Justice is not served by depriving those members of the [AOD] population who are capable of informed consent of the opportunity to participate in research that may be beneficial for themselves and society.”8 Furthermore, doing so would limit the overall scientific benefit of the study findings because they could not be applied to all populations (an issue of external validity). The NIH Revitalization Act of 1993 states that research participants should be representative of the entire population of individuals affected by a certain condition, or likely targets of a tested intervention. The principle of justice assists in striking a balance between protecting vulnerable populations and permitting those populations to benefit from research.9
Beneficence: Risks minimized, benefits maximized
The societal benefits of any research study are dependent on the successful completion and scientific validity of the research process. Consent capacity—both at the point of entry into the research and throughout the protocol—can influence subject retention and ultimately the scientific validity of the research. Subjects who provide consent to participate in research with assured capacity have been found more likely to continue in the research and adhere to its protocols when they are made aware of the risks and benefits clearly at the outset. Both of these factors can increase the likelihood of successful and valid completion of research, thereby ensuring the benefits of the research.10
Respect for Persons: Informed, capable, and autonomous consent
Individuals should be considered capable of making their own decisions; when they are not, they are deserving of additional protections according to the Belmont Report.7 The “Common Rule” guiding the Institutional Review Board (IRB) review process states that “when some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, [IRBs should ensure that] additional safeguards have been included in the study to protect the rights and welfare of these subjects (46.111(b)).”11 Populations with drug dependence are often considered to be vulnerable in that the effects of addiction frequently involve economic hardship, cognitive or psychiatric comorbidities, and incarceration, among other factors that can complicate consent. Appelbaum notes: “The determination of whether patients are competent is critical in striking a proper balance between respecting the autonomy of patients who are capable of making informed decisions and protecting those with cognitive impairment.”12
Determining Consent Capacity
It has been established that the process for assuring subject consent capacity for participation in AOD research can be complex.5 Compounding this complexity is the continuum of research study designs and protocols that the AOD study populations are being asked to consent to. In recognition of these difficulties, The National Institutes of Health—together with other organizations involved or interested in AOD research—provide guidance on addressing consent capacity.13,14,15 Among the most common recommendations is that IRBs and investigators should confirm that capacity is being assessed and not simply assumed and, furthermore, that assessments are commensurate with the cognitive, physiologic, and motivational states of the target population as well as the complexity of the research design and protocol. Moreover, the capacity to consent in populations with AOD dependence may fluctuate; therefore, investigators should take into consideration the need to periodically reevaluate consent capacity.
The importance of and need for more formal and structured approaches to determining a person’s capacity to consent have been readily accepted in clinical care, but the reliability of unstructured judgments of competence by physicians has been proven to be poor.12 Furthermore, states of intoxication or withdrawal, for example, which affect consent capacity, may not always be associated with observable behavior.16 For these and other reasons, numerous approaches and tools have been developed for formally assessing consent capacity.
The available instruments are wide-ranging and vary in the time and the degree of skill and training required for valid administration. Comprehensive reviews of each tool are available in the literature.2,17 Due to the fluctuating nature of consent capacity and the diversity of research protocols, many questions still remain about the reliability and validity of instruments developed for assessing consent capacity.18 According to Appelbaum, “The [MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR)] has been the most widely utilized comprehensive tool for assessing capacity to consent for research, and has thus garnered the most empirical evidence for its reliability and validity.”12,19 However, the MacCAT-CR requires some amount of skill to administer and takes approximately 20 minutes; therefore, it may be infeasible to implement in research settings. The choice of assessment tool or approach must be carefully considered and commensurate with the cognitive state of the subject and the complexity and risk of the research protocol.
In addition to formal assessments of capacity, there are other research procedures that should be considered when attempting to maximize consent capacity, some of which are listed below:
- Avoid recruitment procedures where eligible subjects are likely to be suffering from intoxication, acute withdrawal symptoms, or other situations in which capacity may be diminished.
- Extend the timeframe for the consent process.
- When acceptable, consider the use of research intermediaries20 or identify a legally authorized representative (LAR) who can consent on behalf of a subject.21
- Develop approaches to the consent process that enhance understanding, such as visual presentations or interactive questioning.
- Simplify consent forms and include visual aids where possible.
Because consent capacity is context and decision-specific, strategies for ensuring it among research subjects vary significantly. Decisions about their use should be based on minimally acceptable levels of understanding, appreciation, and reasoning according to the risks and benefits of the research protocol.
1. Rose RM. Informed consent: history, theory, and practice. Am J Otol. 1986;7(1):82–85.
2. Dunn LB, Nowrangi MA, Palmer BW, et al. Assessing decisional capacity for clinical research or treatment: a review of instruments. Am J Psychiatry. 2006;163(8):1323–1334.
3. Baedorf Kassis S, Roth MT. Obtaining Informed Consent for Research from People with Alcohol and Other Drug Dependence. AOD Health. Mar–Apr. 2012. Available at: http://www.bu.edu/aodhealth/issues/issue_mar12/feature32012.html
4. Baedorf Kassis S. Ethical Considerations in Research Using the Drug of Addiction as Treatment: What Can Researchers Learn from Heroin Prescription Studies? AOD Health. Sept–Oct. 2012. Available at: http://www.bu.edu/aodhealth/issues/issue_sept12/feature92012.html
5. Jeste DV, Saks E. Decisional capacity in mental illness and substance use disorders: empirical database and policy implications. Behav Sci Law. 2006;24(4):607–628.
6. Veterans Health Administration National Center for Ethics in Health Care. Ten Myths about Decision-Making Capacity, 2002. Available at: http://www.ethics.va.gov/docs/necrpts/nec_report_20020201_ten_myths_about_dmc.pdf
7. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Bethesda, MD: OHSR, 1979. Available at http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html.
8. Geppert C, Bogenschutz MP. Pharmacological research on addictions: a framework for ethical and policy considerations. J Psychoactive Drugs. 2009;41(1):49–60.
9. Anderson EE, DuBois JM. The need for evidence-based research ethics: a review of the substance abuse literature. Drug Alcohol Depend. 2007;86(2–3):95–105.
10. Del Boca FK, Darkes J. Enhancing the validity and utility of randomized clinical trials in addictions treatment research: II. Participant samples and assessment. Addiction. 2007;102(8):1194–1203.
11. US Department of Health and Human Services: Code of Federal Regulations no. 45 CFR 46 Subpart A, “Common Rule”. Available at: http://www.hhs.gov/ohrp/humansubjects/commonrule/index.html
12. Appelbaum PS. Assessment of patients' competence to consent to treatment. N Engl J Med. 2007;357(18):1834–1840.
13. National Institutes of Health Office of Extramural Research. Research Involving Individuals with Questionable Capacity to Consent: Points to Consider, 2009. Available at: http://grants1.nih.gov/grants/policy/questionablecapacity.htm
14. National Advisory Council on Alcohol Abuse and Alcoholism. Recommended Council guidelines on Ethyl Alcohol Administration in Human Experimentation. Rockville, MD: National Institute on Alcohol Abuse and Alcoholism, 2005.
15. US Department of Health and Human Services Office of Human Research Protections. Institutional Review Board Guidebook, Chapter V, part I. Alcohol and Drug Research. Available at: http://www.hhs.gov/ohrp/archive/irb/irb_chapter5ii.htm
16. Aldridge J, Charles V. Researching the intoxicated: informed consent implications for alcohol and drug research. Drug Alcohol Depend. 2008;93(3):191–196.
17. Sturman ED. The capacity to consent to treatment and research: a review of standardized assessment tools. Clin Psychol Rev. 2005;25(7):954–974.
18. Gurrera RJ, Karel MJ, Azar AR, Moye J. Agreement between instruments for rating treatment decisional capacity. Am J Geriatr Psychiatry. 2007;15(2):168–173.
19. Appelbaum PS, Grisso T. The MacArthur Competence Assessment Tool for Clinical Research. Sarasota: Professional Resource Press, 1996.
20. Festinger DS, Dugosh KL, Croft JR, et al. Do Research Intermediaries Reduce Perceived Coercion to Enter Research Trials Among Criminally Involved Substance Abusers? Ethics Behav. 2011;21(3):252–259.
21. Lambert SF. Ethical and Legal Issues in Addictions Outcome Research. Couns Outcome Res Eval. 2011;2(1) 25–36.